TITLE

Autophagy and Cellular Senescence Mediated by Sox2 Suppress Malignancy of Cancer Cells

AUTHOR(S)
Cho, Yong-Yeon; Kim, Dong Joon; Lee, Hye Suk; Jeong, Chul-Ho; Cho, Eun-Jin; Kim, Myong-Ok; Byun, Sanguine; Lee, Kun-Yeong; Yao, Ke; Carper, Andria; Langfald, Alyssa; Bode, Ann M.; Dong, Zigang
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Autophagy is a critical cellular process required for maintaining cellular homeostasis in health and disease states, but the molecular mechanisms and impact of autophagy on cancer is not fully understood. Here, we found that Sox2, a key transcription factor in the regulation of the “stemness” of embryonic stem cells and induced-pluripotent stem cells, strongly induced autophagic phenomena, including intracellular vacuole formation and lysosomal activation in colon cancer cells. The activation occurred through Sox2-mediated ATG10 gene expression and resulted in the inhibition of cell proliferation and anchorage-independent colony growth ex vivo and tumor growth in vivo. Further, we found that Sox2-induced-autophagy enhanced cellular senescence by up-regulating tumor suppressors or senescence factors, including p16INK4a, p21 and phosphorylated p53 (Ser15). Notably, knockdown of ATG10 in Sox2-expressing colon cancer cells restored cancer cell properties. Taken together, our results demonstrated that regulation of autophagy mediated by Sox2 is a mechanism-driven novel strategy to treat human colon cancers.
ACCESSION #
87625263

 

Related Articles

  • A novel cell type-specific role of p38α in the control of autophagy and cell death in colorectal cancer cells. Comes, F.; Matrone, A.; Lastella, P.; Nico, B.; Susca, F. C.; Bagnulo, R.; Ingravallo, G.; Modica, S.; Lo Sasso, G.; Moschetta, A.; Guanti, G.; Simone, C. // Cell Death & Differentiation;Apr2007, Vol. 14 Issue 4, p693 

    Cancer develops when molecular pathways that control the fine balance between proliferation, differentiation, autophagy and cell death undergo genetic deregulation. The prospects for further substantial advances in the management of colorectal cancer reside in a systematic genetic and functional...

  • Downregulation of Beclin1 and Impairment of Autophagy in a Small Population of Colorectal Cancer. Chen, Zhihong; Li, Yanchun; Zhang, Chi; Yi, Hongmei; Wu, Chang; Wang, Junpu; Liu, Yuwu; Tan, Jieqiong; Wen, Jifang // Digestive Diseases & Sciences;Oct2013, Vol. 58 Issue 10, p2887 

    Background: Autophagy is a highly conserved mechanism for degradation and recycling of long-lived proteins and damaged organelle to maintain cell homeostasis. Deregulation of autophagy has been associated with tumorigenesis. Beclin 1 is an essential autophagy protein and its upregulation has...

  • Pan-Bcl-2 inhibitor Obatoclax is a potent late stage autophagy inhibitor in colorectal cancer cells independent of canonical autophagy signaling. Koehler, Bruno Christian; Jassowicz, Adam; Scherr, Anna-Lena; Lorenz, Stephan; Radhakrishnan, Praveen; Kautz, Nicole; Elssner, Christin; Weiss, Johanna; Jaeger, Dirk; Schneider, Martin; Schulze-Bergkamen, Henning // BMC Cancer;11/19/2015, Vol. 15, p1 

    Background: Colorectal cancer is the third most common malignancy in humans and novel therapeutic approaches are urgently needed. Autophagy is an evolutionarily highly conserved cellular process by which cells collect unnecessary organelles or misfolded proteins and subsequently...

  • Autophagic and tumour suppressor activity of a novel Beclin1-binding protein UVRAG. Chengyu Liang; Pinghui Feng; Bonsu Ku; Dotan, Iris; Canaani, Dan; Byung-Ha Oh; Jung, Jae U. // Nature Cell Biology;Jul2006, Vol. 8 Issue 7, p688 

    Autophagy, the degradation of cytoplasmic components, is an evolutionarily conserved homeostatic process involved in environmental adaptation, lifespan determination and tumour development. The tumor suppressor Beclin1 is part of the PI(3) kinase class III (PI(3)KC3) lipid-kinase complex that...

  • MicroRNA Profiling in Human Colon Cancer Cells during 5-Fluorouracil-Induced Autophagy. Hou, Ni; Han, Jia; Li, Jie; Liu, Yingxun; Qin, Yannan; Ni, Lei; Song, Tusheng; Huang, Chen // PLoS ONE;Dec2014, Vol. 9 Issue 12, p1 

    Autophagy modulation is now recognized as a potential therapeutic approach for cancer (including colorectal cancer), yet the molecular mechanisms regulating autophagy in response to cellular stress are still not well understood. MicroRNAs (miRNAs) have been found to play important roles in...

  • Unspliced XBP1 controls autophagy through FoxO1. Vidal, Rene L; Hetz, Claudio // Cell Research;Apr2013, Vol. 23 Issue 4, p463 

    Protein homeostasis in higher eukaryotes is balanced by a dynamic network of adaptive mechanisms, including the unfolded protein response (UPR) and autophagy. In a paper recently published in Cell Research, Zhu and co-workers uncover a novel biological function of the unspliced form of the UPR...

  • Autophagy: STAT3 maintains order. Du Toit, Andrea // Nature Reviews Molecular Cell Biology;Dec2012, Vol. 13 Issue 12, p754 

    The article discusses the study which examines the role of autophagy in cell homeostasis and cellular response to stress stimuli. The authors have identified a novel mechanism of autophagy repression that involves pro-inflammatory signalling via the signal transducer and activator of...

  • Molecular mechanisms of Nrf2 regulation and how these influence chemical modulation for disease intervention. Harder, Bryan; Tao Jiang; Tongde Wu; Shasha Tao; de la Vega, Montserrat Rojo; Wang Tian; Chapman, Eli; Zhang, Donna D. // Biochemical Society Transactions;8/1/2015, Vol. 43 Issue 4, p680 

    Nrf2 (nuclear factor erytheroid-derived-2-like 2) transcriptional programmes are activated by a variety of cellular stress conditions to maintain cellular homoeostasis. Under non-stress conditions, Nrf2 is under tight regulation by the ubiquitin proteasome system (UPS). Detailed mechanistic...

  • FOXO1 is an essential regulator of pluripotency in human embryonic stem cells. Zhang, Xin; Yalcin, Safak; Lee, Dung-Fang; Yeh, Tsung-Yin J.; Lee, Seung-Min; Su, Jie; Mungamuri, Sathish Kumar; Rimmel�, Pauline; Kennedy, Marion; Sellers, Rani; Landthaler, Markus; Tuschl, Thomas; Chi, Nai-Wen; Lemischka, Ihor; Keller, Gordon; Ghaffari, Saghi // Nature Cell Biology;Sep2011, Vol. 13 Issue 9, p1092 

    Pluripotency of embryonic stem cells (ESCs) is defined by their ability to differentiate into three germ layers and derivative cell types and is established by an interactive network of proteins including OCT4 (also known as POU5F1; ref. ), NANOG (refs , ), SOX2 (ref. ) and their binding...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics