Open Access. Powered by Scholars. Published by Universities.®

Cancer Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Molecular, Cell and Cancer Biology Publications

Discipline
Keyword
Publication Year

Articles 1 - 14 of 14

Full-Text Articles in Cancer Biology

Autophagy-Independent Function Of Atg1 For Apoptosis-Induced Compensatory Proliferation, Mingli Li, Jillian L. Lindblad, Ernesto Perez, Andreas Bergmann, Yun Fan Aug 2016

Autophagy-Independent Function Of Atg1 For Apoptosis-Induced Compensatory Proliferation, Mingli Li, Jillian L. Lindblad, Ernesto Perez, Andreas Bergmann, Yun Fan

Molecular, Cell and Cancer Biology Publications

BACKGROUND: ATG1 belongs to the Uncoordinated-51-like kinase protein family. Members of this family are best characterized for roles in macroautophagy and neuronal development. Apoptosis-induced proliferation (AiP) is a caspase-directed and JNK-dependent process which is involved in tissue repair and regeneration after massive stress-induced apoptotic cell loss. Under certain conditions, AiP can cause tissue overgrowth with implications for cancer.

RESULTS: Here, we show that Atg1 in Drosophila (dAtg1) has a previously unrecognized function for both regenerative and overgrowth-promoting AiP in eye and wing imaginal discs. dAtg1 acts genetically downstream of and is transcriptionally induced by JNK activity, and it is required ...


The Beneficial Role Of Extracellular Reactive Oxygen Species In Apoptosis-Induced Compensatory Proliferation, Neha Diwanji, Andreas Bergmann Aug 2016

The Beneficial Role Of Extracellular Reactive Oxygen Species In Apoptosis-Induced Compensatory Proliferation, Neha Diwanji, Andreas Bergmann

Molecular, Cell and Cancer Biology Publications

Apoptosis-induced proliferation (AiP) maintains tissue homeostasis following massive stress-induced cell death. During this phenomenon, dying cells induce proliferation of the surviving cells to compensate for the tissue loss, and thus restore organ size. Along with wound healing and tissue regeneration, AiP also contributes to tumor repopulation following radiation or chemotherapy. There are several models of AiP. Using an "undead" AiP model that causes hyperplastic overgrowth of Drosophila epithelial tissue, we recently demonstrated that extracellular reactive oxygen species (eROS) are produced by undead epithelial cells, and are necessary for inducing AiP and overgrowth. Furthermore, hemocytes, the Drosophila blood cells, are seen ...


The Unconventional Myosin Crinkled And Its Mammalian Orthologue Myo7a Regulate Caspases In Their Signalling Roles, Mariam H. Orme, Meghana Tare, Andreas Bergmann, Pascal Meier Mar 2016

The Unconventional Myosin Crinkled And Its Mammalian Orthologue Myo7a Regulate Caspases In Their Signalling Roles, Mariam H. Orme, Meghana Tare, Andreas Bergmann, Pascal Meier

Molecular, Cell and Cancer Biology Publications

Caspases provide vital links in non-apoptotic regulatory networks controlling inflammation, compensatory proliferation, morphology and cell migration. How caspases are activated under non-apoptotic conditions and process a selective set of substrates without killing the cell remain enigmatic. Here we find that the Drosophila unconventional myosin CRINKLED (CK) selectively interacts with the initiator caspase DRONC and regulates some of its non-apoptotic functions. Loss of CK in the arista, border cells or proneural clusters of the wing imaginal discs affects DRONC-dependent patterning. Our data indicate that CK acts as substrate adaptor, recruiting SHAGGY46/GSK3-beta to DRONC, thereby facilitating caspase-mediated cleavage and localized modulation ...


P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A. Brekken, Craig W. Vander Kooi, Arthur M. Mercurio Mar 2016

P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A. Brekken, Craig W. Vander Kooi, Arthur M. Mercurio

Molecular, Cell and Cancer Biology Publications

Autocrine VEGF signaling is critical for sustaining prostate and other cancer stem cells (CSCs), and it is a potential therapeutic target, but we observed that CSCs isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Intriguingly, resistance is mediated by VEGF/neuropilin signaling, which is not inhibited by bevacizumab and sunitinib, and it involves the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation. This induction of P-Rex1 is dependent on Myc. CSCs isolated from the PTEN(pc-/-) transgenic model of prostate cancer exhibit Rac1-dependent resistance to bevacizumab. Rac1 inhibition or P-Rex1 downregulation increases ...


Homozygous Knockout Of The Piezo1 Gene In The Zebrafish Is Not Associated With Anemia, Boris E. Shmukler, Nicholas C. Huston, Jonathan N. Thon, Chih-Wen Ni, George Kourkoulis, Nathan D. Lawson, Barry H. Paw, Seth L. Alper Dec 2015

Homozygous Knockout Of The Piezo1 Gene In The Zebrafish Is Not Associated With Anemia, Boris E. Shmukler, Nicholas C. Huston, Jonathan N. Thon, Chih-Wen Ni, George Kourkoulis, Nathan D. Lawson, Barry H. Paw, Seth L. Alper

Molecular, Cell and Cancer Biology Publications

We have now examined the erythroid phenotype in this zebrafish strain carrying a ZFN genomic knockout of piezo1. Genotyping was performed as previously described. In contrast to the anemic phenotype observed in zebrafish subjected to morpholino knockdown of piezo, the genomic ZFN knockout of piezo1 did not segregate either with anemia in the 3-dpf embryo or with dysmorphic erythrocyte morphology in the adult fish.


Nemo Prevents Steatohepatitis And Hepatocellular Carcinoma By Inhibiting Ripk1 Kinase Activity-Mediated Hepatocyte Apoptosis, Vangelis Kondylis, Apostolos Polykratis, Hanno Ehlken, Laura Ochoa-Callejero, Beate Katharina Straub, Santosh Krishna-Subramanian, Trieu-My Van, Harald-Morten Curth, Nicole Heise, Falk Weih, Ulf Klein, Peter Schirmacher, Michelle A. Kelliher, Manolis Pasparakis Nov 2015

Nemo Prevents Steatohepatitis And Hepatocellular Carcinoma By Inhibiting Ripk1 Kinase Activity-Mediated Hepatocyte Apoptosis, Vangelis Kondylis, Apostolos Polykratis, Hanno Ehlken, Laura Ochoa-Callejero, Beate Katharina Straub, Santosh Krishna-Subramanian, Trieu-My Van, Harald-Morten Curth, Nicole Heise, Falk Weih, Ulf Klein, Peter Schirmacher, Michelle A. Kelliher, Manolis Pasparakis

Molecular, Cell and Cancer Biology Publications

IkappaB kinase/necrosis factor kappaB (IKK/NF-kappaB) signaling exhibits important yet opposing functions in hepatocarcinogenesis. Mice lacking NEMO in liver parenchymal cells (LPC) spontaneously develop steatohepatitis and hepatocellular carcinoma (HCC) suggesting that NF-kappaB prevents liver disease and cancer. Here, we show that complete NF-kappaB inhibition by combined LPC-specific ablation of RelA, c-Rel, and RelB did not phenocopy NEMO deficiency, but constitutively active IKK2-mediated NF-kappaB activation prevented hepatocellular damage and HCC in NEMO(LPC-KO) mice. Knock-in expression of kinase inactive receptor-interacting protein kinase 1 (RIPK1) prevented hepatocyte apoptosis and HCC, while RIPK1 ablation induced TNFR1-associated death domain protein (TRADD)-dependent hepatocyte ...


F-Box Protein Fbxo31 Directs Degradation Of Mdm2 To Facilitate P53-Mediated Growth Arrest Following Genotoxic Stress, Sunil K. Malonia, Parul Dutta, Manas Kumar Santra, Michael R. Green Jul 2015

F-Box Protein Fbxo31 Directs Degradation Of Mdm2 To Facilitate P53-Mediated Growth Arrest Following Genotoxic Stress, Sunil K. Malonia, Parul Dutta, Manas Kumar Santra, Michael R. Green

Molecular, Cell and Cancer Biology Publications

The tumor suppressor p53 plays a critical role in maintaining genomic stability. In response to genotoxic stress, p53 levels increase and induce cell-cycle arrest, senescence, or apoptosis, thereby preventing replication of damaged DNA. In unstressed cells, p53 is maintained at a low level. The major negative regulator of p53 is MDM2, an E3 ubiquitin ligase that directly interacts with p53 and promotes its polyubiquitination, leading to the subsequent destruction of p53 by the 26S proteasome. Following DNA damage, MDM2 is degraded rapidly, resulting in increased p53 stability. Because of the important role of MDM2 in modulating p53 function, it is ...


The Creb Coactivator Crtc2 Is A Lymphoma Tumor Suppressor That Preserves Genome Integrity Through Transcription Of Dna Mismatch Repair Genes, Minggang Fang, Magnolia L. Pak, Lynn Chamberlain, Wei Xing, Hongbo Yu, Michael R. Green Jun 2015

The Creb Coactivator Crtc2 Is A Lymphoma Tumor Suppressor That Preserves Genome Integrity Through Transcription Of Dna Mismatch Repair Genes, Minggang Fang, Magnolia L. Pak, Lynn Chamberlain, Wei Xing, Hongbo Yu, Michael R. Green

Molecular, Cell and Cancer Biology Publications

The CREB-regulated transcription coactivator CRTC2 stimulates CREB target gene expression and has a well-established role in modulating glucose and lipid metabolism. Here, we find, unexpectedly, that loss of CRTC2, as well as CREB1 and its coactivator CREB-binding protein (CBP), results in a deficiency in DNA mismatch repair (MMR) and a resultant increased mutation frequency. We show that CRTC2, CREB1, and CBP are transcriptional activators of well-established MMR genes, including EXO1, MSH6, PMS1, and POLD2. Mining of expression profiling databases and analysis of patient samples reveal that CRTC2 and its target MMR genes are downregulated in specific T cell lymphoma subtypes ...


Prostate Tumorigenesis Induced By Pten Deletion Involves Estrogen Receptor Beta Repression, Paul Mak, Jianrong Li, Sanjoy Samanta, Cheng Chang, D. Joseph Jerry, Roger J. Davis, Irwin Leav, Arthur M. Mercurio Mar 2015

Prostate Tumorigenesis Induced By Pten Deletion Involves Estrogen Receptor Beta Repression, Paul Mak, Jianrong Li, Sanjoy Samanta, Cheng Chang, D. Joseph Jerry, Roger J. Davis, Irwin Leav, Arthur M. Mercurio

Molecular, Cell and Cancer Biology Publications

The role of ERbeta in prostate cancer is unclear, although loss of ERbeta is associated with aggressive disease. Given that mice deficient in ERbeta do not develop prostate cancer, we hypothesized that ERbeta loss occurs as a consequence of tumorigenesis caused by other oncogenic mechanisms and that its loss is necessary for tumorigenesis. In support of this hypothesis, we found that ERbeta is targeted for repression in prostate cancer caused by PTEN deletion and that loss of ERbeta is important for tumor formation. ERbeta transcription is repressed by BMI-1, which is induced by PTEN deletion and important for prostate tumorigenesis ...


Resistance To Therapy In Brca2 Mutant Cells Due To Loss Of The Nucleosome Remodeling Factor Chd4, Shawna S. Guillemette, Ryan W. Serra, Min Peng, Janelle A. Hayes, Panagiotis A. Konstantinopoulos, Michael R. Green, Sharon B. Cantor Mar 2015

Resistance To Therapy In Brca2 Mutant Cells Due To Loss Of The Nucleosome Remodeling Factor Chd4, Shawna S. Guillemette, Ryan W. Serra, Min Peng, Janelle A. Hayes, Panagiotis A. Konstantinopoulos, Michael R. Green, Sharon B. Cantor

Molecular, Cell and Cancer Biology Publications

Hereditary cancers derive from gene defects that often compromise DNA repair. Thus, BRCA-associated cancers are sensitive to DNA-damaging agents such as cisplatin. The efficacy of cisplatin is limited, however, by the development of resistance. One cisplatin resistance mechanism is restoration of homologous recombination (HR), which can result from BRCA reversion mutations. However, in BRCA2 mutant cancers, cisplatin resistance can occur independently of restored HR by a mechanism that remains unknown. Here we performed a genome-wide shRNA screen and found that loss of the nucleosome remodeling factor CHD4 confers cisplatin resistance. Restoration of cisplatin resistance is independent of HR but correlates ...


A Laminin 511 Matrix Is Regulated By Taz And Functions As The Ligand For The Alpha6bbeta1 Integrin To Sustain Breast Cancer Stem Cells, Cheng Chang, Hira Lal Goel, Huijie Gao, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Sulev Ingerpuu, Manuel Patarroyo, Shiliang Cao, Elgene Lim, Junhao Mao, Karen Kulju. Mckee, Peter D. Yurchenco, Arthur M. Mercurio Jan 2015

A Laminin 511 Matrix Is Regulated By Taz And Functions As The Ligand For The Alpha6bbeta1 Integrin To Sustain Breast Cancer Stem Cells, Cheng Chang, Hira Lal Goel, Huijie Gao, Bryan M. Pursell, Leonard D. Shultz, Dale L. Greiner, Sulev Ingerpuu, Manuel Patarroyo, Shiliang Cao, Elgene Lim, Junhao Mao, Karen Kulju. Mckee, Peter D. Yurchenco, Arthur M. Mercurio

Molecular, Cell and Cancer Biology Publications

Understanding how the extracellular matrix impacts the function of cancer stem cells (CSCs) is a significant but poorly understood problem. We report that breast CSCs produce a laminin (LM) 511 matrix that promotes self-renewal and tumor initiation by engaging the alpha6Bbeta1 integrin and activating the Hippo transducer TAZ. Although TAZ is important for the function of breast CSCs, the mechanism is unknown. We observed that TAZ regulates the transcription of the alpha5 subunit of LM511 and the formation of a LM511 matrix. These data establish a positive feedback loop involving TAZ and LM511 that contributes to stemness in breast cancer.


De-Regulation Of Jnk And Jak/Stat Signaling In Escrt-Ii Mutant Tissues Cooperatively Contributes To Neoplastic Tumorigenesis, Sarah E. Woodfield, Hillary K. Graves, Jacob Hernandez, Andreas Bergmann Feb 2013

De-Regulation Of Jnk And Jak/Stat Signaling In Escrt-Ii Mutant Tissues Cooperatively Contributes To Neoplastic Tumorigenesis, Sarah E. Woodfield, Hillary K. Graves, Jacob Hernandez, Andreas Bergmann

Molecular, Cell and Cancer Biology Publications

Multiple genes involved in endocytosis and endosomal protein trafficking in Drosophila have been shown to function as neoplastic tumor suppressor genes (nTSGs), including Endosomal Sorting Complex Required for Transport-II (ESCRT-II) components vacuolar protein sorting 22 (vps22), vps25, and vps36. However, most studies of endocytic nTSGs have been done in mosaic tissues containing both mutant and non-mutant populations of cells, and interactions among mutant and non-mutant cells greatly influence the final phenotype. Thus, the true autonomous phenotype of tissues mutant for endocytic nTSGs remains unclear. Here, we show that tissues predominantly mutant for ESCRT-II components display characteristics of neoplastic transformation and ...


Notch Signaling Activates Yorkie Non-Cell Autonomously In Drosophila, Hillary K. Graves, Sarah E. Woodfield, Chih-Chao Yang, Georg Halder, Andreas Bergmann Jun 2012

Notch Signaling Activates Yorkie Non-Cell Autonomously In Drosophila, Hillary K. Graves, Sarah E. Woodfield, Chih-Chao Yang, Georg Halder, Andreas Bergmann

Molecular, Cell and Cancer Biology Publications

In Drosophila imaginal epithelia, cells mutant for the endocytic neoplastic tumor suppressor gene vps25 stimulate nearby untransformed cells to express Drosophila Inhibitor-of-Apoptosis-Protein-1 (DIAP-1), conferring resistance to apoptosis non-cell autonomously. Here, we show that the non-cell autonomous induction of DIAP-1 is mediated by Yorkie, the conserved downstream effector of Hippo signaling. The non-cell autonomous induction of Yorkie is due to Notch signaling from vps25 mutant cells. Moreover, activated Notch in normal cells is sufficient to induce non-cell autonomous Yorkie activity in wing imaginal discs. Our data identify a novel mechanism by which Notch promotes cell survival non-cell autonomously and by which ...


Drosophila Iap1-Mediated Ubiquitylation Controls Activation Of The Initiator Caspase Dronc Independent Of Protein Degradation, Tom V. Lee, Yun Fan, Shiuan Wang, Mayank Srivastava, Meike Broemer, Pascal Meier, Andreas Bergmann Sep 2011

Drosophila Iap1-Mediated Ubiquitylation Controls Activation Of The Initiator Caspase Dronc Independent Of Protein Degradation, Tom V. Lee, Yun Fan, Shiuan Wang, Mayank Srivastava, Meike Broemer, Pascal Meier, Andreas Bergmann

Molecular, Cell and Cancer Biology Publications

Ubiquitylation targets proteins for proteasome-mediated degradation and plays important roles in many biological processes including apoptosis. However, non-proteolytic functions of ubiquitylation are also known. In Drosophila, the inhibitor of apoptosis protein 1 (DIAP1) is known to ubiquitylate the initiator caspase DRONC in vitro. Because DRONC protein accumulates in diap1 mutant cells that are kept alive by caspase inhibition ("undead" cells), it is thought that DIAP1-mediated ubiquitylation causes proteasomal degradation of DRONC, protecting cells from apoptosis. However, contrary to this model, we show here that DIAP1-mediated ubiquitylation does not trigger proteasomal degradation of full-length DRONC, but serves a non-proteolytic function. Our ...