An SLC7A5-dependent nutrient-sensing circuit overcomes cisplatin tolerance via mTOR-autophagy signaling.

Rao P, Zhang T, Li Ju et al. · 2026 · Biochemical and Biophysical Research Communications · Atlas ID RAO2026

What this study shows

A genome-wide CRISPR screen found that mTOR inhibition promotes cisplatin tolerance by activating cytoprotective autophagy — the opposite of the canonical view. SLC7A5 integrates this mTOR-autophagy axis, and leucine supplementation resensitises SLC7A5-expressing tumour cells to cisplatin.

Abstract

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Cisplatin-based chemotherapy responses are heterogeneous across cancers. Using genome-wide CRISPR-Cas9 knockout screening, the authors characterized regulators of cisplatin response and uncovered a counterintuitive finding: mTOR inhibition promotes cisplatin tolerance, contradicting the canonical view that PI3K-AKT-mTOR activation confers chemoresistance. Mechanistically, both mTOR suppression and cisplatin treatment converge to activate cytoprotective autophagy, enhancing cancer cell survival under therapeutic stress.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cancer cell lines (genome-wide CRISPR-Cas9 screen)) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human cancer cell lines (genome-wide CRISPR-Cas9 screen)
Journal	Biochemical and Biophysical Research Communications
Year	2026
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1016/j.bbrc.2026.154478

Extracted findings

Intervention	mTOR inhibition; SLC7A5 knockout; leucine supplementation
Target	SLC7A5; mTOR; autophagy
Model	Human cell lines
Effect	mTOR inhibition increased cisplatin tolerance via cytoprotective autophagy; leucine supplementation restored cisplatin sensitivity

Cite this paper

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Rao, P., et al. (2026). An SLC7A5-dependent nutrient-sensing circuit overcomes cisplatin tolerance via mTOR-autophagy signaling. Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2026.154478

@article{RAO2026,
  author       = {Rao, P. and Zhang, T. and Li Ju and others},
  title        = {{An SLC7A5-dependent nutrient-sensing circuit overcomes cisplatin tolerance via mTOR-autophagy signaling}},
  journal      = {Biochemical and Biophysical Research Communications},
  year         = {2026},
  doi          = {10.1016/j.bbrc.2026.154478},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record RAO2026) [Data set]. https://mtor-atlas.org/study/RAO2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_RAO2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record RAO2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/RAO2026/},
  doi          = {10.5281/zenodo.22059963}
}