LncRNA coordinates Hippo and mTORC1 pathway activation in cancer

Cell Death Dis. 2021 Aug 30;12(9):822. doi: 10.1038/s41419-021-04112-w.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Clone Cells
  • Energy Metabolism
  • Genes, Reporter
  • Hippo Signaling Pathway / genetics*
  • Humans
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Mice
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Regulatory-Associated Protein of mTOR / metabolism
  • Stress, Physiological
  • TOR Serine-Threonine Kinases / metabolism
  • YAP-Signaling Proteins / metabolism

Substances

  • RNA, Long Noncoding
  • RPTOR protein, human
  • Regulatory-Associated Protein of mTOR
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases