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LncRNA coordinates Hippo and mTORC1 pathway activation in cancer

Authors
  • Zhang, Shugeng1
  • Liang, Shuhang1
  • Wu, Dehai1
  • Guo, Hongrui1
  • Ma, Kun1
  • Liu, Lianxin1
  • 1 The First Affiliated Hospital of Harbin Medical University, Harbin, China , Harbin (China)
Type
Published Article
Journal
Cell Death and Disease
Publisher
Springer Nature
Publication Date
Aug 30, 2021
Volume
12
Issue
9
Identifiers
DOI: 10.1038/s41419-021-04112-w
Source
Springer Nature
Disciplines
  • article
License
Green

Abstract

The Hippo and mammalian target of rapamycin complex 1 (mTORC1) pathways are the two predominant pathways that regulate tumour growth and metastasis. Therefore, we explored the potential crosstalk between these two functionally relevant pathways to coordinate their tumour growth-control functions. We found that a Hippo pathway-related long noncoding RNA, HPR, directly interacts with Raptor, an essential component of mTORC1, to upregulate mTORC1 activation by impairing the phosphorylation of Raptor by AMPK. Knockdown or knockout of HPR in breast cancer and cholangiocarcinoma cells led to a reduction in tumour growth. Compared with HPR WT cells, HPR-overexpressing cells exhibited nuclear accumulation of YAP1, and significantly blocked the downregulation of mTORC1 signalling induced by energy stress. Thus, our study reveals a direct link between the Hippo and mTORC1 pathways in the control of tumour growth.

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