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Metastasis

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Articles 1 - 30 of 46

Full-Text Articles in Cancer Biology

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito Jun 2019

Extracellular-Signal Regulated Kinase: A Central Molecule Driving Epithelial-Mesenchymal Transition In Cancer, Monserrat Olea-Flores, Miriam Daniela Zuniga-Eulogio, Miguel Angel Mendoza-Catalan, Hugo Alberto Rodriguez-Ruiz, Eduardo Castaneda-Saucedo, Carlos Ortuno-Pineda, Teresita Padilla-Benavides, Napoleon Navarro-Tito

Open Access Articles

Epithelial-mesenchymal transition (EMT) is a reversible cellular process, characterized by changes in gene expression and activation of proteins, favoring the trans-differentiation of the epithelial phenotype to a mesenchymal phenotype. This process increases cell migration and invasion of tumor cells, progression of the cell cycle, and resistance to apoptosis and chemotherapy, all of which support tumor progression. One of the signaling pathways involved in tumor progression is the MAPK pathway. Within this family, the ERK subfamily of proteins is known for its contributions to EMT. The ERK subfamily is divided into typical (ERK 1/2/5), and atypical (ERK 3/4 ...


Circulating Micrornas Mir-331 And Mir-195 Differentiate Local Luminal A From Metastatic Breast Cancer, Peter Mcanena, Kahraman Tanriverdi, Catherine Curran, K. Gilligan, Jane E. Freedman, James A. L. Brown, Michael J. Kerin May 2019

Circulating Micrornas Mir-331 And Mir-195 Differentiate Local Luminal A From Metastatic Breast Cancer, Peter Mcanena, Kahraman Tanriverdi, Catherine Curran, K. Gilligan, Jane E. Freedman, James A. L. Brown, Michael J. Kerin

Open Access Articles

BACKGROUND: Breast cancer is the leading cause of cancer related death in women, with metastasis the principle cause of mortality. New non-invasive prognostic markers are needed for the early detection of metastasis, facilitating treatment decision optimisation. MicroRNA (miRNA) are small, non-coding RNAs regulating gene expression and involved in many cellular processes, including metastasis. As biomarkers, circulating miRNAs (in blood) hold great promise for informing diagnosis or monitoring treatment responses.

METHODS: Plasma extracted RNA from age matched local Luminal A (n = 4) or metastatic disease (n = 4) were profiled using Next Generation Sequencing. Selected differentially expressed miRNA were validated on a ...


Context Dependent Roles Of Mdmx (Mdm4) And Mdm2 In Breast Cancer Proliferation And Circulating Tumor Cells, Chong Gao May 2019

Context Dependent Roles Of Mdmx (Mdm4) And Mdm2 In Breast Cancer Proliferation And Circulating Tumor Cells, Chong Gao

All Dissertations, Theses, and Capstone Projects

Many human breast cancers overexpress the E3 ubiquitin ligase MDM2 and its homolog MDMX. Expression of MDM2 and MDMX occurs in both estrogen receptor α positive (ER+) and triple negative breast cancer (TNBC). We and others have reported that estrogen activated MDM2 strongly promotes proliferation in ER+ T47D breast cancer cells in a p53-independent manner. Whether MDM2 elicits in vivo p53-independent proliferative functions in T47D breast cancer cells has not been determined. Furthermore it has been shown that ectopic expression of MDM2 targets E-Cadherin for degradation thus leading to increased cell migration and invasion. Therefore we assessed the in vivo ...


Deciphering The Roles Of Δnp63 In Regulating Epithelial To Mesenchymal Transition, Cancer Progression And Metastasis, Ngoc Bui May 2018

Deciphering The Roles Of Δnp63 In Regulating Epithelial To Mesenchymal Transition, Cancer Progression And Metastasis, Ngoc Bui

UT GSBS Dissertations and Theses (Open Access)

p63 is a member of the p53 family, a well-known tumor suppressor which is considered the guardian of the genome. The TP63 gene encodes multiple isoforms that can be categorized into two main isoforms, TAp63 and ΔNp63, which are expressed in different cellular compartments and have distinct functions in many biological processes. While the Flores laboratory identified TAp63 as a tumor and metastasis suppressor, the precise roles of ΔNp63 isoforms in tumorigenesis and metastasis remain elusive. ΔNp63 is the predominant p63 isoform expressed in the epidermis and plays essential roles in regulating epidermal development and homeostasis. Utilizing a ΔNp63-conditional ...


Sphingosine Kinase 1 Regulates Fascin Expression To Promote Metastasis In Triple Negative Breast Cancer, Sunil Acharya May 2018

Sphingosine Kinase 1 Regulates Fascin Expression To Promote Metastasis In Triple Negative Breast Cancer, Sunil Acharya

UT GSBS Dissertations and Theses (Open Access)

Distant metastasis is the primary cause of breast cancer–related mortality. To date, effective therapeutic drugs that target metastasis are still lacking. Triple negative breast cancer (TNBC) occurs in high frequency in young women and are more likely to recur and metastasize than are other breast cancer subtypes. Also, TNBC patients cannot benefit from currently available hormonal or targeted therapies, as they lack estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. Thus, understanding the signaling pathways that promote TNBC metastasis and developing novel therapeutic approaches to target them are critical, in order to prolong the survival and ...


Mtbp Inhibits The Erk1/2-Elk-1 Signaling In Hepatocellular Carcinoma, Atul Ranjan, Swathi V. Iyer, Christopher Ward, Tim Link, Francisco J. Diaz, Animesh Dhar, Ossama W. Tawfik, Steven A. Weinman, Yoshiaki Azuma, Tadahide Izumi, Tomoo Iwakuma Apr 2018

Mtbp Inhibits The Erk1/2-Elk-1 Signaling In Hepatocellular Carcinoma, Atul Ranjan, Swathi V. Iyer, Christopher Ward, Tim Link, Francisco J. Diaz, Animesh Dhar, Ossama W. Tawfik, Steven A. Weinman, Yoshiaki Azuma, Tadahide Izumi, Tomoo Iwakuma

Toxicology and Cancer Biology Faculty Publications

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have performed unbiased luciferase reporter-based signal array analyses and found that MTBP suppresses the activity of the ETS-domain transcription factor Elk-1, a downstream target of Erk1/2 MAP kinases. MTBP also inhibits ...


The Role Of Talin2 In Breast Cancer Tumorigenesis And Metastasis, Liqing Li, Xiang Li, Lei Qi, Piotr G. Rychahou, Naser Jafari, Cai Huang Nov 2017

The Role Of Talin2 In Breast Cancer Tumorigenesis And Metastasis, Liqing Li, Xiang Li, Lei Qi, Piotr G. Rychahou, Naser Jafari, Cai Huang

Markey Cancer Center Faculty Publications

Recent studies show that talin2 has a higher affinity to β-integrin tails and is indispensable for traction force generation and cell invasion. However, its roles in cell migration, cancer cell metastasis and tumorigenesis remain to be determined. Here, we used MDA-MB-231 human breast cancer cells as a model to define the roles of talin2 in cell migration, invasion, metastasis and tumorigenesis. We show here that talin2 knockdown (KD) inhibited cell migration and focal adhesion dynamics, a key step in cell migration, and that talin2 knockout (KO) inhibited cell invasion and traction force generation, the latter is crucial for cell invasion ...


Stabilization Of The Transcription Factors Slug And Twist By The Deubiquitinase Dub3 Is A Key Requirement For Tumor Metastasis, Yiwei Lin, Yu Wang, Qing Shi, Qian Yu, Cuicui Liu, Jing Feng, Jiong Deng, B. Mark Evers, Binhua P. Zhou, Yadi Wu Aug 2017

Stabilization Of The Transcription Factors Slug And Twist By The Deubiquitinase Dub3 Is A Key Requirement For Tumor Metastasis, Yiwei Lin, Yu Wang, Qing Shi, Qian Yu, Cuicui Liu, Jing Feng, Jiong Deng, B. Mark Evers, Binhua P. Zhou, Yadi Wu

Molecular and Cellular Biochemistry Faculty Publications

The Epithelial-mesenchymal transition (EMT) represents a cellular de-differentiation process that provides cells with the increased plasticity required during embryonic development, tissue remodeling, wound healing and metastasis. Slug and Twist are two key EMT transcription factors (EMT-TFs) that are tightly regulated via ubiquitination and degradation. How Slug and Twist escape degradation and become stabilized in cancer cells remains unclear. One plausible mechanism of Slug and Twist stabilization involves removal of ubiquitin by deubiquitinases (DUBs). In this study, we identified Dub3 as a novel DUB for both Slug and Twist. We further found that Dub3 overexpression increased Slug and Twist protein levels ...


The Role Of The Epithelial-To-Mesenchymal Transition (Emt) In Lung Cancer Progression, David H. Peng Aug 2017

The Role Of The Epithelial-To-Mesenchymal Transition (Emt) In Lung Cancer Progression, David H. Peng

UT GSBS Dissertations and Theses (Open Access)

Lung cancer is the leading cause of cancer-related deaths due to conventional therapy resistance and metastatic disease, therefore understanding the mechanisms governing these biological functions is vital for improving patient survival. Approximately 30% of patients with the adenocarcinoma histologic subset of lung cancer possess an activating KRAS mutation, characterized by a lack of response to chemotherapies with a poor overall 5-year survival rate. Despite the mutational frequency, KRAS remains a challenge to pharmacologically inhibit and current drugs undergoing clinical trials that target specific downstream effector proteins of KRAS, such as MEK inhibitors, have failed to produce significant clinical benefits. Previous ...


The Regulation Of Snail: On The Ubiquitin Edge, Qian Yu, Binhua P. Zhou, Yadi Wu Jul 2017

The Regulation Of Snail: On The Ubiquitin Edge, Qian Yu, Binhua P. Zhou, Yadi Wu

Pharmacology and Nutritional Sciences Faculty Publications

Metastasis accounts for a majority of cancer death. One key feature during metastasis is epithelial-mesenchymal transition (EMT), which is regulated by transcription factors such as Snail and Twist. In non-malignant cells, Snail has a short half-life and is degraded via ubiquitination, but its stability is increased in cancer cell. However, the mechanism by which Snail escapes ubiquitination and degradation remains unknown. Recently, we found that Dub3 is a deubiquinase of Snail. Most importantly, we determined that Dub3 responded to extracellular signals such as IL-6, and that the resultant signaling prevented Snail degradation, and promoted cancer growth, invasion, and migration. In ...


A Mechanistic Investigation Of Insulin Receptor Substrate 2 Function In Breast Cancer Progression, Jose R. Mercado-Matos Jun 2017

A Mechanistic Investigation Of Insulin Receptor Substrate 2 Function In Breast Cancer Progression, Jose R. Mercado-Matos

GSBS Dissertations and Theses

The advancement of cancer treatment depends on understanding the biological processes that contribute to disease progression. The spread of tumor cells from the primary site to distant organs is the biggest obstacle to efficacious treatment. The insulin receptor substrate (IRS) proteins IRS1 and IRS2 are cytoplasmic adaptor proteins that organize signaling events downstream of the Insulin receptor (IR) and the Insulin-like growth factor receptor 1 (IGF1R). Both of these receptors have been implicated in cancer progression. The IRS proteins share a significant level of homology and are both capable of recruiting and activating phosphatidylinositol-3 kinase (PI3K). Despite these similarities, signaling ...


Nuak1 Has Tumor Suppressive Activity In Epithelial Ovarian Cancer, Parima Saxena Jun 2017

Nuak1 Has Tumor Suppressive Activity In Epithelial Ovarian Cancer, Parima Saxena

Electronic Thesis and Dissertation Repository

NUAK1, a downstream substrate of the stress metabolism regulator Liver kinase B1 (LKB1), has been implicated as an oncogene and tumor suppressor, with distinct roles in cell cycle, senescence and cell adhesion. Epithelial ovarian cancer (EOC) spheroids remain dormant during intraperitoneal metastasis with reduced proliferation and metabolism to survive metabolically harsh conditions, possibly implicating a role of NUAK1 in EOC spheroid biology. I hypothesize that NUAK1 is regulated by LKB1 to promote dormancy in EOC. I demonstrate that NUAK1 expression and phosphorylation is regulated by LKB1 in EOC cell lines. NUAK1 is largely under-expressed in many established and new ascites-derived ...


Primary Lung Carcinoid Metastatic To The Breast, Marianna Zagurovskaya, Karen Tran-Harding, Richard Gibbs Jun 2017

Primary Lung Carcinoid Metastatic To The Breast, Marianna Zagurovskaya, Karen Tran-Harding, Richard Gibbs

Radiology Faculty Publications

Lung carcinoid tumors account for approximately 2% of lung cancers, with 10% of the tumors represented by the atypical type. While atypical carcinoids are metastatic to intrathoracic lymph nodes in approximately half of the cases on the initial presentation, distant metastases are seen in only 20% of the patients and are found most frequently in bones, liver, adrenal glands, and brain. We present a case of an unusual metastatic disease to the breast in 51-year-old female who developed a new breast mass 2 years after left lower lobectomy due to atypical carcinoid tumor. Atypical pulmonary carcinoid metastases to the breast ...


The Role Of Semaphorin 5a In Pancreatic Cancer Progression And Metastasis, Sugandha Saxena Dr. May 2017

The Role Of Semaphorin 5a In Pancreatic Cancer Progression And Metastasis, Sugandha Saxena Dr.

Theses & Dissertations

Pancreatic cancer (PC) is an aggressive disease with an overall 5-year survival rate of less than 7%, statistics that have not changed in almost five decades. Metastasis is one of the leading causes of mortality in PC. Accumulating evidence suggests that axon guidance molecules, such as semaphorins, are involved in cancer progression, invasion, and metastasis. Recent genomic characterization of pancreatic ductal adenocarcinoma revealed aberration in axon guidance pathway genes as well. Previous reports from our laboratory have identified one such molecule Semaphorin5A (SEMA5A) as a putative cell adhesion molecule which is involved in organ-specific homing during PC metastasis. My dissertation ...


Rna-Sequencing Reveals Direct Targets Of Tumor Suppressor Mir-203 In Human Mammary Epithelial Cells, Alexander P. Boardman, Victoria E. Pedanou, Tessa M. Simone, Michael R. Green May 2017

Rna-Sequencing Reveals Direct Targets Of Tumor Suppressor Mir-203 In Human Mammary Epithelial Cells, Alexander P. Boardman, Victoria E. Pedanou, Tessa M. Simone, Michael R. Green

Senior Scholars Program

Background: Breast cancer is the leading cause of cancer-related mortality in women worldwide. Since a significant portion of cases present with or progress to metastatic disease, furthering our understanding of metastasis is critical to develop better treatments. Epithelial cells maintain contact with the extracellular matrix (ECM) predominantly via integrin engagement, a process required for tissue integrity and barrier function. In non-transformed cells, loss of ECM adhesion promotes a specialized form of programmed cell death, anoikis. In order for efficient metastasis to occur, breast tumor cells must evade anoikis. miR-203, known to be down-regulated in several cancers, was found by our ...


Fluorinated N,N'-Diarylureas As Novel Therapeutic Agents Against Cancer Stem Cells, Dasha E. Kenlan, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers May 2017

Fluorinated N,N'-Diarylureas As Novel Therapeutic Agents Against Cancer Stem Cells, Dasha E. Kenlan, Piotr G. Rychahou, Vitaliy M. Sviripa, Heidi L. Weiss, Chunming Liu, David S. Watt, B. Mark Evers

Markey Cancer Center Faculty Publications

Colorectal cancer is the second-leading cause of cancer-related mortality in the United States. More than 50% of patients with colorectal cancer will develop local recurrence or distant organ metastasis. Cancer stem cells play a major role in the survival and metastasis of cancer cells. In this study, we examined the effects of novel AMP-activated protein kinase (AMPK) activating compounds on colorectal cancer metastatic and stem cell lines as potential candidates for chemotherapy. We found that activation of AMPK by all fluorinated N,N-diarylureas (FND) compounds at micromolar levels significantly inhibited the cell-cycle progression and subsequent cellular proliferation. In addition, we ...


Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang Dec 2016

Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang

UT GSBS Dissertations and Theses (Open Access)

Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important ...


Foxc2 Augments Tumor Propagation And Metastasis In Osteosarcoma, Maricel C. Gozol, Dongyu Jia, Paul-Joseph Aspuria, Dong-Joo Cheon, Naoyuki Miura, Ann E. Walts, Beth Y. Karlan, Sandra Orsulic Aug 2016

Foxc2 Augments Tumor Propagation And Metastasis In Osteosarcoma, Maricel C. Gozol, Dongyu Jia, Paul-Joseph Aspuria, Dong-Joo Cheon, Naoyuki Miura, Ann E. Walts, Beth Y. Karlan, Sandra Orsulic

Dongyu Jia

Osteosarcoma is a highly malignant tumor that contains a small subpopulation of tumor-propagating cells (also known as tumor-initiating cells) characterized by drug resistance and high metastatic potential. The molecular mechanism by which tumor-propagating cells promote tumor growth is poorly understood. Here, we report that the transcription factor forkhead box C2 (FOXC2) is frequently expressed in human osteosarcomas and is important in maintaining osteosarcoma cells in a stem-like state. In osteosarcoma cell lines, we show that anoikis conditions stimulate FOXC2 expression. Downregulation of FOXC2 decreases anchorage-independent growth and invasion in vitro and lung metastasis in vivo, while overexpression of FOXC2 increases ...


Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez Aug 2016

Investigating The Roles Of Δnp63 As A Suppressor Of Migration, Invasion, And Metastasis, Ramon E. Flores Gonzalez

UT GSBS Dissertations and Theses (Open Access)

Cancer is one of the leading causes of death and disease in the world. Considerable resources are spent to study and understand cancer, with the hope of developing new treatments and eventually cures that will help millions of people. Efforts to understand cancer are hindered by its inherent complexity and instability. Nonetheless, understanding the basics of tumor development and progression are the key to focused on studying the role of ΔNp63 in cancer, a p53 family member known to be involved in epithelial development, microRNA biogenesis, and stem cell maintenance. Using the strength of in vivo mouse models, we found ...


Influencing Pathways That Cause Metastasis And Stemness In Epithelial Ovarian Cancer, Alyse Lynn Huisken-Hill Jun 2016

Influencing Pathways That Cause Metastasis And Stemness In Epithelial Ovarian Cancer, Alyse Lynn Huisken-Hill

Electronic Theses, Projects, and Dissertations

Ovarian cancer is the fifth leading cause of cancer death in women between the ages of 35 and 74. With 22 thousand new cases and 15 thousand deaths annually ovarian cancer is among the most deadly cancers with a death to incidence ratio of 68%. With 70% of cases High Grade Serous Ovarian Carcinoma (HGSOC) is the most common type of ovarian cancer and causes 90% of ovarian cancer deaths. 80% of patients have reoccurrence within five years and only 15-30% of patients with recurrent metastatic ovarian cancer respond to current therapies, chemotherapy and surgery. One reason for the high ...


Role Of Cell Type And Genetic Alterations In Driving Breast Cancer Pathogenesis, Divya Bhagirath May 2016

Role Of Cell Type And Genetic Alterations In Driving Breast Cancer Pathogenesis, Divya Bhagirath

Theses & Dissertations

Breast cancer is the second most leading cause of death among women in the United States. Several environmental and genetic factors contribute to the pathogenesis of the disease. It is classified into different subtypes based on expression of certain markers as well as that of set of genes that define the disease progression and associated mortality. Identification of various subtypes namely: Luminal-like (Luminal-A, Luminal-B), ErbB2 over-expressing, Basal-like and Claudin low types, showed an association of survival outcomes with that of the corresponding gene expression signatures, thus paving a way for therapeutic intervention. It further emphasizes the importance of nature of ...


Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong Apr 2016

Oncolytic Virus Therapy For The Treatment Of Metastatic Ovarian Cancer, Jessica Tong

Electronic Thesis and Dissertation Repository

The management of patients with epithelial ovarian cancer (EOC) faces two major challenges which standard treatments fail to effectively address: 1) Diffuse metastasis as a consequence of late stage diagnosis and 2) intra-tumoral heterogeneity, which fuels tumor evolution and drives the acquisition of chemotherapeutic resistance. In this thesis, we tested new therapeutic strategies using a 3-dimensional in vitro spheroid culture model that mimics key steps of epithelial ovarian cancer metastasis; and another model that mimics both temporal and cellular heterogeneity by establishing multiple cell lines from a single patient over the course of disease progression. Using these models, we investigated ...


Exploring The Regulation And Function Of Epithelial-Mesenchymal Plasticity In Ovarian Cancer Spheroids, Samah Rafehi Apr 2016

Exploring The Regulation And Function Of Epithelial-Mesenchymal Plasticity In Ovarian Cancer Spheroids, Samah Rafehi

Electronic Thesis and Dissertation Repository

Epithelial-mesenchymal transition (EMT) serves as a key mechanism driving tumour cell migration, invasion, and metastasis in many carcinomas. Transforming growth factor-beta (TGFβ) signalling is implicated in several steps during cancer pathogenesis and acts as a classical inducer of EMT. Since epithelial ovarian cancer (EOC) cells have the potential to switch between epithelial and mesenchymal states during metastasis, we predicted that modulation of TGFβ signalling would significantly impact EMT and the malignant potential of EOC spheroid cells. Ovarian cancer patient ascites-derived cells naturally underwent an EMT response when aggregating into spheroids, and this was reversed upon spheroid re-attachment to a substratum ...


Stromal Fibroblasts Facilitate Cancer Cell Invasion By A Novel Invadopodia-Independent Matrix Degradation Process, Hong Cao, Robbin Eppinga, Gina L. Razidio, Eugene W. Krueger, Jing Chen, Li Qiang, Mark A. Mcniven Mar 2016

Stromal Fibroblasts Facilitate Cancer Cell Invasion By A Novel Invadopodia-Independent Matrix Degradation Process, Hong Cao, Robbin Eppinga, Gina L. Razidio, Eugene W. Krueger, Jing Chen, Li Qiang, Mark A. Mcniven

Faculty Work Comprehensive List

Metastatic invasion of tumors into peripheral tissues is known to rely upon protease-mediated degradation of the surrounding stroma. This remodeling process utilizes complex, actin-based, specializations of the plasma membrane termed invadopodia that act both to sequester and release matrix metalloproteinases. Here we report that cells of mesenchymal origin, including tumor-associated fibroblasts, degrade substantial amounts of surrounding matrix by a mechanism independent of conventional invadopodia. These degradative sites lack the punctate shape of conventional invadopodia to spread along the cell base and are reticular and/or fibrous in character. In marked contrast to invadopodia, this degradation does not require the action ...


Increasing The Stability And Expression Of Green Fluorescent Protein In Pancreatic Cancer Cells For Metastasis Assays, Holly M. Ross, John F. Harms Jan 2016

Increasing The Stability And Expression Of Green Fluorescent Protein In Pancreatic Cancer Cells For Metastasis Assays, Holly M. Ross, John F. Harms

Honors Projects and Presentations: Undergraduate

Pancreatic cancer is the fourth leading cause of cancer death in the United States, with only 11% of patients diagnosed with metastatic disease surviving the first year. Even so, few studies exist to characterize the mechanism of metastasis in this highly aggressive form of cancer. Consequently, it is imperative that techniques, such as tagging cells with green fluorescent protein (GFP), are developed to track cancerous cells over the course of their spread. Unfortunately, the existing GFP vector contains a cytomegalovirus promotor, which is readily silenced by cells and decreases the vector’s usefulness for long-term studies in vivo. It was ...


The Role Of Tumor Suppressor Co-Chaperone Chip/Stub1 In Erbb2-Mediated Oncogenesis, Haitao Luan Dec 2015

The Role Of Tumor Suppressor Co-Chaperone Chip/Stub1 In Erbb2-Mediated Oncogenesis, Haitao Luan

Theses & Dissertations

The epidermal growth factor receptor (EGFR) family member ErbB2 (Her2) is overexpressed in 20 -30% of invasive breast cancers and this overexpression correlates with poor prognosis and shorter overall as well as disease-free survival. Aberrant expression of ErbB2 through gene amplification, transcriptional deregulation and/or altered endocytic trafficking results in overexpression of ErbB2 at the plasma membrane and biases ErbB2 from primarily ligand-driven hetero-dimerization under normal expression conditions to increased ligand-independent homo-dimer and hetero-dimer formation and consequent activation. C-terminus of HSC70-Inteeracting protein (CHIP)/STIP1-homologous U-Box containing protein 1 (STUB1) is an HSP90/HSC70 interacting negative co-chaperone known to promote ubiquitination ...


Suboptimal Cytoreduction In Ovarian Carcinoma Is Associated With Molecular Pathways Characteristic Of Increased Stromal Activation, Zhenqiu Liu, Jessica A. Beach, Hasmik Agadjanian, Dongyu Jia, Paul-Joseph Aspuria, Beth Y. Karlan, Sandra Orsulic Nov 2015

Suboptimal Cytoreduction In Ovarian Carcinoma Is Associated With Molecular Pathways Characteristic Of Increased Stromal Activation, Zhenqiu Liu, Jessica A. Beach, Hasmik Agadjanian, Dongyu Jia, Paul-Joseph Aspuria, Beth Y. Karlan, Sandra Orsulic

Dongyu Jia

Objective: Suboptimal cytoreductive surgery in advanced epithelial ovarian cancer (EOC) is associated with poor survival but it is unknown if poor outcome is due to the intrinsic biology of unresectable tumors or insufficient surgical effort resulting in residual tumor-sustaining clones. Our objective was to identify the potential molecular pathway(s) and cell type(s) that may be responsible for suboptimal surgical resection.
Methods: By comparing gene expression in optimally and suboptimally cytoreduced patients, we identified a gene network associated with suboptimal cytoreduction and explored the biological processes and cell types associated with this gene network.
Results: We show that primary ...


The Role Of Endothelin 3 In Melanoma Progression And Metastasis, Nikeisha L. Chin Nov 2015

The Role Of Endothelin 3 In Melanoma Progression And Metastasis, Nikeisha L. Chin

FIU Electronic Theses and Dissertations

Endothelin receptor b (Ednrb) and its ligand Endothelin 3 (Edn3) have been implicated in melanoma. Several studies have shown an upregulation of EDNRB and EDN3 at both the protein and mRNA levels, as melanoma becomes more aggressive. This study investigated the putative role played by Edn3 over-expression in melanoma progression and angiogenesis in vivo. We crossed Tg(Grm1)Epv transgenic mice that aberrantly express metabotropic glutamate receptor1 under the Dopachrome tautomerase promoter, leading to spontaneous melanocytic lesions in the ears and tails that do not metastasize, with transgenics that overexpress Edn3 under the Keratin 5 promoter (K5-Edn3) or overexpress Ednrb ...


Clinical And Experimental Importance Of Circulating Tumor Cells In Prostate Cancer, Lori Lowes Sep 2015

Clinical And Experimental Importance Of Circulating Tumor Cells In Prostate Cancer, Lori Lowes

Electronic Thesis and Dissertation Repository

Prostate cancer (PCa) remains a leading cause of death in men, primarily due to ineffective treatment in the metastatic setting. During this phase of PCa, circulating tumor cells (CTCs) are shed into the bloodstream and their presence and number are important in patient prognosis. The CellSearch® system (CSS) is the only U.S. Food and Drug Administration (FDA) and Health Canada approved instrument for detection of CTCs, making it the current clinical gold standard in CTC technology. Although the CSS provides a minimally invasive means of patient monitoring in the metastatic setting, little is known about the role of CTCs ...


The Lung Microenvironment Influences The Metastatic Behaviour Of Breast Cancer Cells In An Innovative 3d Ex Vivo Pulmonary Metastasis Model, Matt M. Piaseczny Jun 2015

The Lung Microenvironment Influences The Metastatic Behaviour Of Breast Cancer Cells In An Innovative 3d Ex Vivo Pulmonary Metastasis Model, Matt M. Piaseczny

Electronic Thesis and Dissertation Repository

Lung metastasis remains a leading cause of death in breast cancer patients. This study established an innovative 3D ex vivo pulmonary metastasis assay (PuMA) to test the hypothesis that the lung microenvironment promotes metastatic behaviour of whole population and stem-like ALDHhiCD44+ breast cancer cells. Following in vivo delivery of breast cancer cells to mice, lungs were excised, maintained in culture and imaged to observe breast cancer growth over time. We observed metastatic progression of breast cancer cells in the PuMA, most notably of ALDHhiCD44+ cells which progressed rapidly from single cells to multicellular colonies over 21 ...