RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1

Loss of function of tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) leads to the activation of mammalian target of rapamycin complex 1 (mTORC1). Hyperactivated mTORC1 plays a critical role in tumor growth, but the underlying mechanism is still not completely elucidated. Here, by analyzing Tsc1- or...

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Autores principales:	Wei Lin, Xiaofeng Wan, Anjiang Sun, Meng Zhou, Xu Chen, Yanling Li, Zixi Wang, Hailiang Huang, Hongwu Li, Xianguo Chen, Juan Hua, Xiaojun Zha
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	mTOR STAT3 RUNX1 EGFR tuberous sclerosis complex tumorigenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/67595c2674834a9192202460a32169d2
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spelling	oai:doaj.org-article:67595c2674834a9192202460a32169d22021-11-14T04:34:26ZRUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC12372-770510.1016/j.omto.2021.10.009https://doaj.org/article/67595c2674834a9192202460a32169d22021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2372770521001467https://doaj.org/toc/2372-7705Loss of function of tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) leads to the activation of mammalian target of rapamycin complex 1 (mTORC1). Hyperactivated mTORC1 plays a critical role in tumor growth, but the underlying mechanism is still not completely elucidated. Here, by analyzing Tsc1- or Tsc2-null mouse embryonic fibroblasts, rat Tsc2-null ELT3 cells, and human cancer cells, we present evidence for the involvement of epidermal growth factor receptor (EGFR) as a downstream target of mTORC1 in tumor growth. We show that mTORC1 leads to increased EGFR expression through upregulation of runt-related transcriptional factor 1 (RUNX1). Knockdown of EGFR impairs proliferation and tumoral growth of Tsc-deficient cells, while overexpression of EGFR promotes the proliferation of the control cells. Moreover, the mTOR signaling pathway has been shown to be positively correlated with EGFR in human cancers. In addition, we demonstrated that EGFR enhances cell growth through activation of signal transducer and activator of transcription 3 (STAT3). We conclude that activation of the RUNX1/EGFR/STAT3 signaling pathway contributes to tumorigenesis caused by hyperactivated mTORC1 and should be targeted for the treatment of mTORC1-related tumors, particularly TSC.Wei LinXiaofeng WanAnjiang SunMeng ZhouXu ChenYanling LiZixi WangHailiang HuangHongwu LiXianguo ChenJuan HuaXiaojun ZhaElsevierarticlemTORSTAT3RUNX1EGFRtuberous sclerosis complextumorigenesisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Therapy: Oncolytics, Vol 23, Iss , Pp 387-401 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mTOR STAT3 RUNX1 EGFR tuberous sclerosis complex tumorigenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	mTOR STAT3 RUNX1 EGFR tuberous sclerosis complex tumorigenesis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Wei Lin Xiaofeng Wan Anjiang Sun Meng Zhou Xu Chen Yanling Li Zixi Wang Hailiang Huang Hongwu Li Xianguo Chen Juan Hua Xiaojun Zha RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1
description	Loss of function of tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) leads to the activation of mammalian target of rapamycin complex 1 (mTORC1). Hyperactivated mTORC1 plays a critical role in tumor growth, but the underlying mechanism is still not completely elucidated. Here, by analyzing Tsc1- or Tsc2-null mouse embryonic fibroblasts, rat Tsc2-null ELT3 cells, and human cancer cells, we present evidence for the involvement of epidermal growth factor receptor (EGFR) as a downstream target of mTORC1 in tumor growth. We show that mTORC1 leads to increased EGFR expression through upregulation of runt-related transcriptional factor 1 (RUNX1). Knockdown of EGFR impairs proliferation and tumoral growth of Tsc-deficient cells, while overexpression of EGFR promotes the proliferation of the control cells. Moreover, the mTOR signaling pathway has been shown to be positively correlated with EGFR in human cancers. In addition, we demonstrated that EGFR enhances cell growth through activation of signal transducer and activator of transcription 3 (STAT3). We conclude that activation of the RUNX1/EGFR/STAT3 signaling pathway contributes to tumorigenesis caused by hyperactivated mTORC1 and should be targeted for the treatment of mTORC1-related tumors, particularly TSC.
format	article
author	Wei Lin Xiaofeng Wan Anjiang Sun Meng Zhou Xu Chen Yanling Li Zixi Wang Hailiang Huang Hongwu Li Xianguo Chen Juan Hua Xiaojun Zha
author_facet	Wei Lin Xiaofeng Wan Anjiang Sun Meng Zhou Xu Chen Yanling Li Zixi Wang Hailiang Huang Hongwu Li Xianguo Chen Juan Hua Xiaojun Zha
author_sort	Wei Lin
title	RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1
title_short	RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1
title_full	RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1
title_fullStr	RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1
title_full_unstemmed	RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1
title_sort	runx1/egfr pathway contributes to stat3 activation and tumor growth caused by hyperactivated mtorc1
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/67595c2674834a9192202460a32169d2
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RUNX1/EGFR pathway contributes to STAT3 activation and tumor growth caused by hyperactivated mTORC1

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