Autophagy regulates the stemness of cervical cancer stem cells

Yi Yang,1,2 Li Yu,1 Jin Li,1 Ya Hong Yuan,1 Xiao Li Wang,1 Shi Rong Yan,1 Dong Sheng Li,1 Yan Ding1 1Hubei Key Laboratory of Embryonic Stem Cell Research, 2Reproductive Center, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China Abstract: Cancer stem cells (CSC...

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Autores principales: Yang Y, Yu L, Li J, Yuan YH, Wang XL, Yan SR, Li DS, Ding Y
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Lenguaje:EN
Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:1bb2052aad394a379e2626d36f09e22b2021-12-02T00:15:32ZAutophagy regulates the stemness of cervical cancer stem cells1177-5491https://doaj.org/article/1bb2052aad394a379e2626d36f09e22b2017-06-01T00:00:00Zhttps://www.dovepress.com/autophagy-regulates-the-stemness-of-cervical-cancer-stem-cells-peer-reviewed-article-BTThttps://doaj.org/toc/1177-5491Yi Yang,1,2 Li Yu,1 Jin Li,1 Ya Hong Yuan,1 Xiao Li Wang,1 Shi Rong Yan,1 Dong Sheng Li,1 Yan Ding1 1Hubei Key Laboratory of Embryonic Stem Cell Research, 2Reproductive Center, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China 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: cervical cancer, autophagy, cancer stem cell, LC3, Oct4Yang YYu LLi JYuan YHWang XLYan SRLi DSDing YDove Medical Pressarticlecervical cancerautophagycancer stem cellMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol Volume 11, Pp 71-79 (2017)
institution DOAJ
collection DOAJ
language EN
topic cervical cancer
autophagy
cancer stem cell
Medicine (General)
R5-920
spellingShingle cervical cancer
autophagy
cancer stem cell
Medicine (General)
R5-920
Yang Y
Yu L
Li J
Yuan YH
Wang XL
Yan SR
Li DS
Ding Y
Autophagy regulates the stemness of cervical cancer stem cells
description Yi Yang,1,2 Li Yu,1 Jin Li,1 Ya Hong Yuan,1 Xiao Li Wang,1 Shi Rong Yan,1 Dong Sheng Li,1 Yan Ding1 1Hubei Key Laboratory of Embryonic Stem Cell Research, 2Reproductive Center, Taihe Hospital, Hubei University of Medicine, Shiyan, People’s Republic of China 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: cervical cancer, autophagy, cancer stem cell, LC3, Oct4
format article
author Yang Y
Yu L
Li J
Yuan YH
Wang XL
Yan SR
Li DS
Ding Y
author_facet Yang Y
Yu L
Li J
Yuan YH
Wang XL
Yan SR
Li DS
Ding Y
author_sort Yang Y
title Autophagy regulates the stemness of cervical cancer stem cells
title_short Autophagy regulates the stemness of cervical cancer stem cells
title_full Autophagy regulates the stemness of cervical cancer stem cells
title_fullStr Autophagy regulates the stemness of cervical cancer stem cells
title_full_unstemmed Autophagy regulates the stemness of cervical cancer stem cells
title_sort autophagy regulates the stemness of cervical cancer stem cells
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/1bb2052aad394a379e2626d36f09e22b
work_keys_str_mv AT yangy autophagyregulatesthestemnessofcervicalcancerstemcells
AT yul autophagyregulatesthestemnessofcervicalcancerstemcells
AT lij autophagyregulatesthestemnessofcervicalcancerstemcells
AT yuanyh autophagyregulatesthestemnessofcervicalcancerstemcells
AT wangxl autophagyregulatesthestemnessofcervicalcancerstemcells
AT yansr autophagyregulatesthestemnessofcervicalcancerstemcells
AT lids autophagyregulatesthestemnessofcervicalcancerstemcells
AT dingy autophagyregulatesthestemnessofcervicalcancerstemcells
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