Leucyl-tRNA synthetase 1 is required for proliferation of TSC-null cells

Uncontrolled cell proliferation associated with cancer depends on the functional abrogation of at least one of tumor suppressor. In response to nutrient cue, tuberous sclerosis complex (TSC) works as a tumor suppressor which inhibits cell growth via negative regulation of the mammalian target of rapamycin complex (mTORC1). However, the regulation mechanism of nutrient-dependent cell proliferation in TSC-null cells remains unclear. Here, we demonstrate that leucine is required for cell proliferation through the activation of leucyl-tRNA synthetase (LARS1)-mTORC1 pathway in TSC-null cells. Cell proliferation and survival were attenuated by LARS1 knock-down or inhibitors in TSC-null cells. In addition, either rapa-mycin or LARS1 inhibitors significantly decreased colony formation ability while their combined treat-ment drastically attenuated it. Taken together, we suggest that LARS1 inhibitors might considered as novel tools for the regression of tumor growth and proliferation in TSC-null tumor cells which regrow upon discontinuation of the mTORC1 inhibition. (c) 2021 Published by Elsevier Inc.

Automated summary

In TSC-null cells, leucine is essential for cell proliferation through the activation of LARS1-mTORC1 pathway, and LARS1 inhibitors may be considered as novel tools for reversing tumor growth and proliferation in TSC-null tumor cells.