Rxivist logo

Profiling the surface proteome identifies actionable biology for TSC1 mutant cells beyond mTORC1 signaling

By Junnian Wei, Kevin K. Leung, Charles Truillet, Davide Ruggero, James A Wells, Michael J. Evans

Posted 01 Aug 2018
bioRxiv DOI: 10.1101/382929

Loss of the TSC1/TSC2 complex leads to constitutively high mTORC1 signaling; however, pharmacological inhibition of mTORC1 in this setting produces a broad spectrum of clinical responses. We report herein several cell surface proteins upregulated by inactivation of TSC1 that present therapeutic alternatives or adjuvants to direct mTORC1 inhibition. A proteomics screen revealed that TSC1 loss most dramatically induced the expression of neprilysin (NEP/CD10) and aminopeptidase N (APN/CD13). The survival of TSC1 null human cancer cells was dependent on NEP expression, and TSC1 mutation sensitized cells to biochemical inhibition of APN. Remarkably, NEP and APN upregulation occurred via a TSC2- and mTORC1-independent mechanism; therefore, the antiproliferative effects of mTORC1 inhibition could be augmented by co-suppression of APN activity.

Download data

  • Downloaded 445 times
  • Download rankings, all-time:
    • Site-wide: 38,425 out of 94,912
    • In cancer biology: 1,224 out of 3,367
  • Year to date:
    • Site-wide: 51,434 out of 94,912
  • Since beginning of last month:
    • Site-wide: 34,070 out of 94,912

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)