title: Autophagy and cellular senescence mediated by Sox2 suppress malignancy of cancer cells.
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 p16(INK4a), 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.
authors: College of Pharmacy, The Catholic University of Korea, Gyeonggi-do, Korea. yongyeon@catholic.ac.kr
authors: Yong-Yeon
authors: YY
authors: Cho
authors: Dong Joon
authors: DJ
authors: Kim
authors: Hye Suk
authors: HS
authors: Lee
authors: Chul-Ho
authors: CH
authors: Jeong
authors: Eun-Jin
authors: EJ
authors: Cho
authors: Myong-Ok
authors: MO
authors: Kim
authors: Sanguine
authors: S
authors: Byun
authors: Kun-Yeong
authors: KY
authors: Lee
authors: Ke
authors: K
authors: Yao
authors: Andria
authors: A
authors: Carper
authors: Alyssa
authors: A
authors: Langfald
authors: Ann M
authors: AM
authors: Bode
authors: Zigang
authors: Z
authors: Dong
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000502:physiology*; D006801:Humans; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000502:physiology*; D015398:Signal Transduction; D014183:Transplantation, Heterologous
chemical_list: C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt