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

被引：37

作者：

Cho, Yong-Yeon ^{[2
]}

Kim, Dong Joon ^{[1
]}

Lee, Hye Suk ^{[2
]}

Jeong, Chul-Ho ^{[1
]}

Cho, Eun-Jin ^{[1
]}

Kim, Myong-Ok ^{[1
]}

Byun, Sanguine ^{[1
]}

Lee, Kun-Yeong ^{[1
]}

Yao, Ke ^{[1
]}

Carper, Andria ^{[1
]}

Langfald, Alyssa ^{[1
]}

Bode, Ann M. ^{[1
]}

Dong, Zigang ^{[1
]}

机构：

[1] Univ Minnesota, Hormel Inst, Austin, MN 55912 USA

[2] Catholic Univ Korea, Coll Pharm, Gyeonggi Do, South Korea

来源：

PLOS ONE | 2013年 / 8卷 / 02期

基金：

美国国家卫生研究院;

关键词：

INHIBITION; INDUCTION; GROWTH; DEATH; PTEN; PLURIPOTENCY; MECHANISMS; PHENOTYPE; APOPTOSIS; PATHWAY;

D O I：

10.1371/journal.pone.0057172

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

共 49 条

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