Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer

Abstract Rab1A, as a highly conserved small guanosine triphosphatase (GTPase), plays contentious roles in different types of cancers. The role of Rab1A in colorectal cancer (CRC) has been described in previous studies, but the molecular mechanisms of Rab1A in CRC remain far from being addressed. In...

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Autores principales:	Chaozhong Peng, Xiao Li, Zhixue Ye, Wenqing Wu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e6de7cc7fea3490293d0197c5c84d410
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spelling	oai:doaj.org-article:e6de7cc7fea3490293d0197c5c84d4102021-12-02T19:06:29ZRab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer10.1038/s41598-021-95798-72045-2322https://doaj.org/article/e6de7cc7fea3490293d0197c5c84d4102021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95798-7https://doaj.org/toc/2045-2322Abstract Rab1A, as a highly conserved small guanosine triphosphatase (GTPase), plays contentious roles in different types of cancers. The role of Rab1A in colorectal cancer (CRC) has been described in previous studies, but the molecular mechanisms of Rab1A in CRC remain far from being addressed. In the present study, we found that Rab1A expression was significantly upregulated in CRC tissues and increased Rab1A expression correlated with tumor size, lymph node metastasis (LNM) and tumor-node-metastasis (TNM) stage of CRC patients. We also found that Rab1A exerts its promotive effect on CRC cell proliferation, migration and EMT progress. Further mechanistic experiments showed that glioma-associated oncogene-1 (Gli1), as a key transcriptional factor of the Hedgehog pathway, was implicated in Rab1A-mediated regulation of CRC cell proliferation and migration. In addition, Rab1A upregulated Gli1 expression through Smoothened homolog (SMO)-independent pathway. Finally, Rab1A activated mechanistic target of rapamycin (mTOR) signaling in CRC cells. Collectively, our results define Rab1A as a novel regulator of Gli1 to promote CRC cell proliferation and migration, and suggest that the Rab1A/mTOR/Gli1 axis may serve as a promising therapeutic target for the treatment of CRC.Chaozhong PengXiao LiZhixue YeWenqing WuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chaozhong Peng Xiao Li Zhixue Ye Wenqing Wu Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer
description	Abstract Rab1A, as a highly conserved small guanosine triphosphatase (GTPase), plays contentious roles in different types of cancers. The role of Rab1A in colorectal cancer (CRC) has been described in previous studies, but the molecular mechanisms of Rab1A in CRC remain far from being addressed. In the present study, we found that Rab1A expression was significantly upregulated in CRC tissues and increased Rab1A expression correlated with tumor size, lymph node metastasis (LNM) and tumor-node-metastasis (TNM) stage of CRC patients. We also found that Rab1A exerts its promotive effect on CRC cell proliferation, migration and EMT progress. Further mechanistic experiments showed that glioma-associated oncogene-1 (Gli1), as a key transcriptional factor of the Hedgehog pathway, was implicated in Rab1A-mediated regulation of CRC cell proliferation and migration. In addition, Rab1A upregulated Gli1 expression through Smoothened homolog (SMO)-independent pathway. Finally, Rab1A activated mechanistic target of rapamycin (mTOR) signaling in CRC cells. Collectively, our results define Rab1A as a novel regulator of Gli1 to promote CRC cell proliferation and migration, and suggest that the Rab1A/mTOR/Gli1 axis may serve as a promising therapeutic target for the treatment of CRC.
format	article
author	Chaozhong Peng Xiao Li Zhixue Ye Wenqing Wu
author_facet	Chaozhong Peng Xiao Li Zhixue Ye Wenqing Wu
author_sort	Chaozhong Peng
title	Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer
title_short	Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer
title_full	Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer
title_fullStr	Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer
title_full_unstemmed	Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer
title_sort	rab1a promotes cell proliferation and migration by upregulating gli1 in colorectal cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e6de7cc7fea3490293d0197c5c84d410
work_keys_str_mv	AT chaozhongpeng rab1apromotescellproliferationandmigrationbyupregulatinggli1incolorectalcancer AT xiaoli rab1apromotescellproliferationandmigrationbyupregulatinggli1incolorectalcancer AT zhixueye rab1apromotescellproliferationandmigrationbyupregulatinggli1incolorectalcancer AT wenqingwu rab1apromotescellproliferationandmigrationbyupregulatinggli1incolorectalcancer
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Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer

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