CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression

Abstract LIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumor progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. The chaperonin protein containing TCP1 (CCT) is a cellular molecular chaperone complex, which is necessary for...

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Autores principales: Qing Liao, Yun Ren, Yuyi Yang, Xiaohui Zhu, Yunfei Zhi, Yujie Zhang, Yi Chen, Yanqing Ding, Liang Zhao
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Publicado: Nature Publishing Group 2021
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Acceso en línea:https://doaj.org/article/8cbca934e7c942eb9cb35a1908afd967
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spelling oai:doaj.org-article:8cbca934e7c942eb9cb35a1908afd9672021-12-05T12:10:56ZCCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression10.1038/s41389-021-00374-32157-9024https://doaj.org/article/8cbca934e7c942eb9cb35a1908afd9672021-12-01T00:00:00Zhttps://doi.org/10.1038/s41389-021-00374-3https://doaj.org/toc/2157-9024Abstract LIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumor progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. The chaperonin protein containing TCP1 (CCT) is a cellular molecular chaperone complex, which is necessary for the correct folding of many proteins. It contains eight subunits, CCT1-8. CCT8 is overexpressed in many cancers, however, studies on CCT8 are limited and its role on CRC development and progression remains elusive. In this study, we confirmed that CCT8 and LASP1 can interact with each other and express positively in CRC cells. CCT8 could recover the ability of LASP1 to promote the invasion of CRC; CCT8 could significantly promote the proliferation, invasion, and metastasis of colorectal cells in vivo and in vitro. Mechanically, CCT8 inhibited the entry of WTp53 into the nucleus, and there was a negative correlation between the expression of CCT8 and the nuclear expression of WTp53 in clinical colorectal tissues. CCT8 promoted the cell cycle evolution and EMT progression of CRC by inhibiting the entry of WTp53 into the nucleus. Clinically, CCT8 was highly expressed in CRC. More importantly, the overall survival of CRC patients with high expression of CCT8 was worse than that of patients with low expression of CCT8. These findings indicate that as LASP1-modulated proteins, CCT8 plays a key role in promoting the progression of colorectal cancer, which provides a potential target for clinical intervention in patients with colorectal cancer.Qing LiaoYun RenYuyi YangXiaohui ZhuYunfei ZhiYujie ZhangYi ChenYanqing DingLiang ZhaoNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENOncogenesis, Vol 10, Iss 12, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Qing Liao
Yun Ren
Yuyi Yang
Xiaohui Zhu
Yunfei Zhi
Yujie Zhang
Yi Chen
Yanqing Ding
Liang Zhao
CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression
description Abstract LIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumor progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. The chaperonin protein containing TCP1 (CCT) is a cellular molecular chaperone complex, which is necessary for the correct folding of many proteins. It contains eight subunits, CCT1-8. CCT8 is overexpressed in many cancers, however, studies on CCT8 are limited and its role on CRC development and progression remains elusive. In this study, we confirmed that CCT8 and LASP1 can interact with each other and express positively in CRC cells. CCT8 could recover the ability of LASP1 to promote the invasion of CRC; CCT8 could significantly promote the proliferation, invasion, and metastasis of colorectal cells in vivo and in vitro. Mechanically, CCT8 inhibited the entry of WTp53 into the nucleus, and there was a negative correlation between the expression of CCT8 and the nuclear expression of WTp53 in clinical colorectal tissues. CCT8 promoted the cell cycle evolution and EMT progression of CRC by inhibiting the entry of WTp53 into the nucleus. Clinically, CCT8 was highly expressed in CRC. More importantly, the overall survival of CRC patients with high expression of CCT8 was worse than that of patients with low expression of CCT8. These findings indicate that as LASP1-modulated proteins, CCT8 plays a key role in promoting the progression of colorectal cancer, which provides a potential target for clinical intervention in patients with colorectal cancer.
format article
author Qing Liao
Yun Ren
Yuyi Yang
Xiaohui Zhu
Yunfei Zhi
Yujie Zhang
Yi Chen
Yanqing Ding
Liang Zhao
author_facet Qing Liao
Yun Ren
Yuyi Yang
Xiaohui Zhu
Yunfei Zhi
Yujie Zhang
Yi Chen
Yanqing Ding
Liang Zhao
author_sort Qing Liao
title CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression
title_short CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression
title_full CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression
title_fullStr CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression
title_full_unstemmed CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression
title_sort cct8 recovers wtp53-suppressed cell cycle evolution and emt to promote colorectal cancer progression
publisher Nature Publishing Group
publishDate 2021
url https://doaj.org/article/8cbca934e7c942eb9cb35a1908afd967
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