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Critical role of SOX2–IGF2 signaling in aggressiveness of bladder cancer

Signaling elicited by the stem cell factors SOX2, OCT4, KLF4, and MYC not only mediates reprogramming of differentiated cells to pluripotency but has also been correlated with tumor malignancy. In this study, we found SOX2 expression signifies poor recurrence-free survival and correlates with advanc...

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Autores principales: Chiu, Yu-Fan, Wu, Chia-Chang, Kuo, Ming-Han, Miao, Chia-Cheng, Zheng, Ming-Yi, Chen, Pei-Yu, Lin, Sheng-Chieh, Chang, Junn-Liang, Wang, Yuan-Hung, Chou, Yu-Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237425/
https://www.ncbi.nlm.nih.gov/pubmed/32427884
http://dx.doi.org/10.1038/s41598-020-65006-z
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author Chiu, Yu-Fan
Wu, Chia-Chang
Kuo, Ming-Han
Miao, Chia-Cheng
Zheng, Ming-Yi
Chen, Pei-Yu
Lin, Sheng-Chieh
Chang, Junn-Liang
Wang, Yuan-Hung
Chou, Yu-Ting
author_facet Chiu, Yu-Fan
Wu, Chia-Chang
Kuo, Ming-Han
Miao, Chia-Cheng
Zheng, Ming-Yi
Chen, Pei-Yu
Lin, Sheng-Chieh
Chang, Junn-Liang
Wang, Yuan-Hung
Chou, Yu-Ting
author_sort Chiu, Yu-Fan
collection PubMed
description Signaling elicited by the stem cell factors SOX2, OCT4, KLF4, and MYC not only mediates reprogramming of differentiated cells to pluripotency but has also been correlated with tumor malignancy. In this study, we found SOX2 expression signifies poor recurrence-free survival and correlates with advanced pathological grade in bladder cancer. SOX2 silencing attenuated bladder cancer cell growth, while its expression promoted cancer cell survival and proliferation. Under low-serum stress, SOX2 expression promoted AKT phosphorylation and bladder cancer cells’ spheroid-forming capability. Furthermore, pharmacological inhibition of AKT phosphorylation, using MK2206, inhibited the SOX2-mediated spheroid formation of bladder cancer cells. Gene expression profiling showed that SOX2 expression, in turn, induced IGF2 expression, while SOX2 silencing inhibited IGF2 expression. Moreover, knocking down IGF2 and IGF1R diminished bladder cancer cell growth. Lastly, pharmacological inhibition of IGF1R, using linsitinib, also inhibited the SOX2-mediated spheroid formation of bladder cancer cells under low-serum stress. Our findings indicate the SOX2–IGF2 signaling affects the aggressiveness of bladder cancer cell growth. This signaling could be a promising biomarker and therapeutic target for bladder cancer intervention.
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spelling pubmed-72374252020-05-29 Critical role of SOX2–IGF2 signaling in aggressiveness of bladder cancer Chiu, Yu-Fan Wu, Chia-Chang Kuo, Ming-Han Miao, Chia-Cheng Zheng, Ming-Yi Chen, Pei-Yu Lin, Sheng-Chieh Chang, Junn-Liang Wang, Yuan-Hung Chou, Yu-Ting Sci Rep Article Signaling elicited by the stem cell factors SOX2, OCT4, KLF4, and MYC not only mediates reprogramming of differentiated cells to pluripotency but has also been correlated with tumor malignancy. In this study, we found SOX2 expression signifies poor recurrence-free survival and correlates with advanced pathological grade in bladder cancer. SOX2 silencing attenuated bladder cancer cell growth, while its expression promoted cancer cell survival and proliferation. Under low-serum stress, SOX2 expression promoted AKT phosphorylation and bladder cancer cells’ spheroid-forming capability. Furthermore, pharmacological inhibition of AKT phosphorylation, using MK2206, inhibited the SOX2-mediated spheroid formation of bladder cancer cells. Gene expression profiling showed that SOX2 expression, in turn, induced IGF2 expression, while SOX2 silencing inhibited IGF2 expression. Moreover, knocking down IGF2 and IGF1R diminished bladder cancer cell growth. Lastly, pharmacological inhibition of IGF1R, using linsitinib, also inhibited the SOX2-mediated spheroid formation of bladder cancer cells under low-serum stress. Our findings indicate the SOX2–IGF2 signaling affects the aggressiveness of bladder cancer cell growth. This signaling could be a promising biomarker and therapeutic target for bladder cancer intervention. Nature Publishing Group UK 2020-05-19 /pmc/articles/PMC7237425/ /pubmed/32427884 http://dx.doi.org/10.1038/s41598-020-65006-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chiu, Yu-Fan
Wu, Chia-Chang
Kuo, Ming-Han
Miao, Chia-Cheng
Zheng, Ming-Yi
Chen, Pei-Yu
Lin, Sheng-Chieh
Chang, Junn-Liang
Wang, Yuan-Hung
Chou, Yu-Ting
Critical role of SOX2–IGF2 signaling in aggressiveness of bladder cancer
title Critical role of SOX2–IGF2 signaling in aggressiveness of bladder cancer
title_full Critical role of SOX2–IGF2 signaling in aggressiveness of bladder cancer
title_fullStr Critical role of SOX2–IGF2 signaling in aggressiveness of bladder cancer
title_full_unstemmed Critical role of SOX2–IGF2 signaling in aggressiveness of bladder cancer
title_short Critical role of SOX2–IGF2 signaling in aggressiveness of bladder cancer
title_sort critical role of sox2–igf2 signaling in aggressiveness of bladder cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237425/
https://www.ncbi.nlm.nih.gov/pubmed/32427884
http://dx.doi.org/10.1038/s41598-020-65006-z
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