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Invasion

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Articles 1 - 17 of 17

Full-Text Articles in Cancer Biology

Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito Aug 2019

Leptin Promotes Expression Of Emt-Related Transcription Factors And Invasion In A Src And Fak-Dependent Pathway In Mcf10a Mammary Epithelial Cells, Monserrat Olea-Flores, Miriam Zuñiga-Eulogio, Arvey Tacuba-Saavedra, Magdalena Bueno-Salgado, Andrea Sánchez-Carvajal, Yovani Vargas-Santiago, Miguel A. Mendoza-Catalán, Eduardo Pérez Salazar, Alejandra García-Hernández, Teresita Padilla-Benavides, Napoleón Navarro-Tito

University of Massachusetts Medical School Faculty Publications

Leptin is one of the main adipokines secreted in breast tissue, and has been associated with epithelial-mesenchymal transition (EMT) and tumor progression in breast cancer. Leptin promotes EMT, cell migration and invasion in epithelial breast cells, leading to tumor progression. However, the molecular mechanism that underlies these events is not fully understood; however, the activation of different signaling pathways appears to be essential. In this sense, the effect of leptin on the activation of kinases like Src and FAK, which regulate signaling pathways that activate the EMT program, has not been completely described. Therefore, we investigated the involvement of these ...


Microrna-29a Activates A Multi-Component Growth And Invasion Program In Glioblastoma, Yun Zhao, Wei Huang, Tae-Min Kim, Yuchae Jung, Lata G. Menon, Hongyan Xing, Hongwei Li, Rona S. Carroll, Peter J. Park, Hong Wei Yang, Mark D. Johnson Jan 2019

Microrna-29a Activates A Multi-Component Growth And Invasion Program In Glioblastoma, Yun Zhao, Wei Huang, Tae-Min Kim, Yuchae Jung, Lata G. Menon, Hongyan Xing, Hongwei Li, Rona S. Carroll, Peter J. Park, Hong Wei Yang, Mark D. Johnson

Open Access Articles

BACKGROUND: Glioblastoma is a malignant brain tumor characterized by rapid growth, diffuse invasion and therapeutic resistance. We recently used microRNA expression profiles to subclassify glioblastoma into five genetically and clinically distinct subclasses, and showed that microRNAs both define and contribute to the phenotypes of these subclasses. Here we show that miR-29a activates a multi-faceted growth and invasion program that promotes glioblastoma aggressiveness.

METHODS: microRNA expression profiles from 197 glioblastomas were analyzed to identify the candidate miRNAs that are correlated to glioblastoma aggressiveness. The candidate miRNA, miR-29a, was further studied in vitro and in vivo.

RESULTS: Members of the miR-29 subfamily ...


Identification Of A Novel Invasion-Promoting Region In Insulin Receptor Substrate 2, Jose Mercado-Matos, Jenny Janusis, Sha Zhu, Samuel S. Chen, Leslie M. Shaw Jun 2018

Identification Of A Novel Invasion-Promoting Region In Insulin Receptor Substrate 2, Jose Mercado-Matos, Jenny Janusis, Sha Zhu, Samuel S. Chen, Leslie M. Shaw

University of Massachusetts Medical School Faculty Publications

Although the insulin receptor substrate (IRS) proteins IRS1 and IRS2 share considerable homology and activate common signaling pathways, their contributions to breast cancer are distinct. IRS1 has been implicated in the proliferation and survival of breast tumor cells. In contrast, IRS2 facilitates glycolysis, invasion, and metastasis. To determine the mechanistic basis for IRS2-dependent functions, we investigated unique structural features of IRS2 that are required for invasion. Our studies revealed that the ability of IRS2 to promote invasion is dependent upon upstream insulin-like growth factor 1 receptor (IGF-1R)/insulin receptor (IR) activation and the recruitment and activation of phosphatidylinositol 3-kinase (PI3K ...


Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther Nov 2017

Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther

Nicole Porther

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases ...


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 ...


Micrornas Of The Mir-17~92 Cluster Regulate Multiple Aspects Of Pancreatic Tumor Development And Progression, Brian J. Quattrochi, Anushree Gulvady, David R. Driscoll, Makoto Sano, David S. Klimstra, Christopher E. Turner, Brian C. Lewis May 2017

Micrornas Of The Mir-17~92 Cluster Regulate Multiple Aspects Of Pancreatic Tumor Development And Progression, Brian J. Quattrochi, Anushree Gulvady, David R. Driscoll, Makoto Sano, David S. Klimstra, Christopher E. Turner, Brian C. Lewis

Open Access Articles

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by resistance to currently employed chemotherapeutic approaches. Members of the mir-17~92 cluster of microRNAs (miRNAs) are upregulated in PDAC, but the precise roles of these miRNAs in PDAC are unknown. Using genetically engineered mouse models, we show that loss of mir-17~92 reduces ERK pathway activation downstream of mutant KRAS and promotes the regression of KRASG12D-driven precursor pancreatic intraepithelial neoplasias (PanINs) and their replacement by normal exocrine tissue. In a PDAC model driven by concomitant KRASG12D expression and Trp53 heterozygosity, mir-17~92 deficiency extended the survival of mice that lacked ...


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 ...


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 ...


Mien1 Drives Breast Cancer Invasion By Regulating Cytoskeletal-Focal Adhesions Dynamics, Marilyne F. Kpetemey B.S. May 2015

Mien1 Drives Breast Cancer Invasion By Regulating Cytoskeletal-Focal Adhesions Dynamics, Marilyne F. Kpetemey B.S.

Theses and Dissertations

In the recent years, Migration and Invasion Enhancer 1(MIEN1) has emerged as a potential biomarker and a plausible target in breast cancer. Located in the 17q12-21 region of the human chromosome, next to the Her-2/neu loci, MIEN1 presents a robust expression in breast carcinomas; however is completely absent or low in the normal tissues. MIEN1 is post-translationally modified by geranyl-geranyl transferase-I (GgtaseI), which adds isoprenyl group to the carboxyl-terminal of the protein. Prenylated MIEN1 then associates with the inner leaflet of the plasma membrane and acts as an adaptor protein triggering downstream signaling through the Akt/NF-kB axis ...


Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther Mar 2015

Intracellular Signaling And Trafficking In Cancer: Role Of Rab5-Gtpase In Migration And Invasion Of Breast Cells, Nicole Porther

FIU Electronic Theses and Dissertations

Metastasis is characterized pathologically by uncontrolled cell invasion, proliferation, migration and angiogenesis. Steroid hormones, such as estrogen, and growth factors, which include insulin growth factor I/II (IGF-1/IGF-2) therapy has been associated with most if not all of the features of metastasis. It has been determined that IGF-1 increases cell survival of cancer cells and potentiate the effect of E2 and other ligand growth factors on breast cancer cells. However not much information is available that comprehensively expounds on the roles of insulin growth factor receptor (IGFR) and Rab GTPases may play in breast cancer. The latter, Rab GTPases ...


Requirements Of Rab5 Activity In Highly Invasive Breast Cancer Cell Lines, Nicole Porther, M Alejandro Barbieri Dec 2013

Requirements Of Rab5 Activity In Highly Invasive Breast Cancer Cell Lines, Nicole Porther, M Alejandro Barbieri

Nicole Porther

Rab5 expression in cancer has been associated with the disease progression and prognosis. We have previously shown that growth factor-directed cell invasion and migration was dependent on Rab5 activation in non-invasive breast cancer cells. However, hardly any data is available regarding the role of Rab5 in invasive cells in the presence of growth factor.  In our present study, we report that the invasive and migratory properties of the highly invasive breast cancer cell line, MDAMB-231, were abrogated in cells expressing the inactive (GDP-bound) form of Rab5 irrespective of growth factor stimulation; while the invasive potential of breast cancer cell lines ...


Timp-2 Decreases The Invasive Potential Of Mcf-7 And Mdamb-231 Cells Independent Of Mmp Inhibition, Mario Cepeda Dec 2012

Timp-2 Decreases The Invasive Potential Of Mcf-7 And Mdamb-231 Cells Independent Of Mmp Inhibition, Mario Cepeda

Electronic Thesis and Dissertation Repository

Tissue Inhibitors of Metalloproteinases (TIMPs) are the natural inhibitors of Matrix Metalloproteinases (MMPs), a family of proteins primarily responsible for Extracellular Matrix (ECM) remodeling. TIMP-2 is a special member of the TIMP family as it is both an inhibitor and promoter of MMP activity, and can also bind the cell surface and signal inside the cell to influence cell behavior. In this study, MDAMB-231 and MCF-7 breast cancer cells were treated with physiological concentration of TIMP-2, which decreased the invasive potential of both cell lines. This was independent of MMP inhibition, and instead a decrease in the expression and secretion ...


The Embryonic Protein Nodal Supports Metastatic Phenotypes In Breast Cancer, Daniela F. Quail Jun 2012

The Embryonic Protein Nodal Supports Metastatic Phenotypes In Breast Cancer, Daniela F. Quail

Electronic Thesis and Dissertation Repository

Metastasis is the process by which tumour cells disseminate to distant organ sites. Aberrant expression of stem cell-associated proteins within tumours is associated with metastasis and poor patient prognosis. One example of a stem cell factor that is associated with cancer progression is Nodal, a member of the TGF-β superfamily. Nodal is normally limited to pluripotent stem cells during embryonic development, and to specialized dynamic adult tissue (such as the cycling endometrium), but is aberrantly re-expressed in multiple cancer types, including melanoma, glioma, prostate cancer, and pancreatic cancer. The central objective of this thesis is to determine the role of ...


The Role Of Receptor Tyrosine Kinase Axl In Pancreatic Ductal Adenocarcinoma And Its Regulation By Hematopoietic Progenitor Kinase 1, Xianzhou Song Dec 2011

The Role Of Receptor Tyrosine Kinase Axl In Pancreatic Ductal Adenocarcinoma And Its Regulation By Hematopoietic Progenitor Kinase 1, Xianzhou Song

UT GSBS Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies with less than 5% of five year survival rate. New molecular markers and new therapeutic targets are urgently needed for patients with PDA. Oncogenic receptor tyrosine kinase Axl has been reported to be overexpressed in many types of human malignancies, including diffuse glioma, melanoma, osteosarcoma, and carcinomas of lung, colon, prostate, breast, ovary, esophagus, stomach, and kidney. However, the expression and functions of Axl in PDA are unclear. We hypothesized that Axl contributes to the development and progression of PDA. We examined Axl expression in 54 human PDA samples ...


Mcam/Muc18 Regulates Melanoma Progression By Modulating The Expression Of Id-1, Maya Zigler Dec 2010

Mcam/Muc18 Regulates Melanoma Progression By Modulating The Expression Of Id-1, Maya Zigler

UT GSBS Dissertations and Theses (Open Access)

The acquisition of the metastatic melanoma phenotype is associated with increased expression of the melanoma cell adhesion molecule MCAM/MUC18 (CD146). However, the mechanism by which MUC18 contributes to melanoma metastasis remains unclear. Herein, we stably silenced MUC18 expression utilizing lentivirus-incorporated small hairpin RNA, in two metastatic melanoma cell lines, A375SM and C8161, and conducted cDNA microarray analysis. We identified and validated that the transcriptional regulator, Inhibitor of DNA Binding-1 (Id-1), previously shown to function as an oncogene in several malignancies, was downregulated by 5.6-fold following MUC18 silencing. Additionally, we found that MUC18 regulated Id-1 expression at the transcriptional ...


Cip4 And Src In Promoting The Migration And Invasion Of Breast Cancers, Christina S. Pichot May 2010

Cip4 And Src In Promoting The Migration And Invasion Of Breast Cancers, Christina S. Pichot

UT GSBS Dissertations and Theses (Open Access)

Cellular invasion represents a critical early step in the metastatic cascade, and many proteins have been identified as part of an “invasive signature.” The non-receptor tyrosine kinase Src is commonly upregulated in breast cancers, often in conjunction with overexpression of EGFR. Signaling from this pathway stimulates cell proliferation, migration, and invasion and frequently involves proteins that regulate the cytoskeleton. My data demonstrates that inhibition of Src, using the small-molecule inhibitor dasatinib, impairs cellular migration and invasion. Furthermore, Src inhibition sensitizes the cells to the effects of the chemotherapeutic doxorubicin resulting in dramatic, synergistic inhibition of proliferation with combination treatments. The ...


Prostasin Is Expressed In Benign Prostatic Hyperplasia And Regulates Cell Proliferation And Invasion Via Inos, Icam-1, And Cycli, Meghan Hatfield Jan 2008

Prostasin Is Expressed In Benign Prostatic Hyperplasia And Regulates Cell Proliferation And Invasion Via Inos, Icam-1, And Cycli, Meghan Hatfield

Electronic Theses and Dissertations

Prostasin is expressed in normal prostate epithelial cells but down-regulated in prostate cancers, while prostasin re-expression in invasive prostate cancer cells reduced invasion. We examined prostasin expression and function in benign prostatic hyperplasia (BPH). We evaluated prostasin expression in 12 BPH specimens by immunohistochemistry, and evaluated the impact of prostasin silencing by siRNA on the expression of the inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), and cyclin D1, as well as on cell proliferation and invasion, using the BPH-1 human prostate epithelial cell line model. Prostasin expression was localized in the glands of BPH tissues by immunohistochemistry, in ...