Autophagy regulates the stemness of cervical cancer stem cells.

Yi Yang, Li Yu, Jin Li, Ya Hong Yuan, Xiao Li Wang, Shi Rong Yan, Dong Sheng Li, Yan Ding
Author Information
  1. Yi Yang: Hubei Key Laboratory of Embryonic Stem Cell Research.
  2. Li Yu: Hubei Key Laboratory of Embryonic Stem Cell Research.
  3. Jin Li: Hubei Key Laboratory of Embryonic Stem Cell Research.
  4. Ya Hong Yuan: Hubei Key Laboratory of Embryonic Stem Cell Research.
  5. Xiao Li Wang: Hubei Key Laboratory of Embryonic Stem Cell Research.
  6. Shi Rong Yan: Hubei Key Laboratory of Embryonic Stem Cell Research.
  7. Dong Sheng Li: Hubei Key Laboratory of Embryonic Stem Cell Research.
  8. Yan Ding: Hubei Key Laboratory of Embryonic Stem Cell Research.

Abstract

Cancer stem cells (CSCs) are a rare population of multipotent cells with the capacity to self-renew. It has been reported that there are CSCs in cervical cancer cells. Pluripotency-associated (PA) transcription factors such as Oct4, Sox2, Nanog and CD44 have been used to isolate CSCs subpopulations. In this study, we showed that autophagy plays an important role in the biological behavior of cervical cancer cells. The expression of the autophagy protein Beclin 1 and LC3B was higher in tumorspheres established from human cervical cancers cell lines (and CaSki) than in the parental adherent cells. It was also observed that the basal and starvation-induced autophagy flux was higher in tumorspheres than in the bulk population. Autophagy could regulate the expression level of PA proteins in cervical CSCs. In addition, CRISPR/Cas 9-mediated Beclin 1 knockout enhanced the malignancy of HeLa cells, leading to accumulation of PA proteins and promoted tumorsphere formation. Our findings suggest that autophagy modulates homeostasis of PA proteins, and Beclin 1 is critical for CSC maintenance and tumor development in nude mice. This demonstrates that a prosurvival autophagic pathway is critical for CSC maintenance.

Keywords

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Word Cloud

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