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

Yong Yeon Cho, Dong Joon Kim, Hye Suk Lee, Chul Ho Jeong, Eun Jin Cho, Myong Ok Kim, Sanguine Byun, Kun Yeong Lee, Ke Yao, Andria Carper, Alyssa Langfald, Ann M. Bode, Zigang Dong

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32 Citations (Scopus)

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.

Original languageEnglish
Article numbere57172
JournalPloS one
Volume8
Issue number2
DOIs
Publication statusPublished - 2013 Feb 25

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Cho, Y. Y., Kim, D. J., Lee, H. S., Jeong, C. H., Cho, E. J., Kim, M. O., Byun, S., Lee, K. Y., Yao, K., Carper, A., Langfald, A., Bode, A. M., & Dong, Z. (2013). Autophagy and Cellular Senescence Mediated by Sox2 Suppress Malignancy of Cancer Cells. PloS one, 8(2), [e57172]. https://doi.org/10.1371/journal.pone.0057172