The Adaptation of Cancer Cells to Serum Deprivation Is Mediated by mTOR-Dependent Cholesterol Synthesis
Ilyassova B. Rakhimgerey N. Rakhimova S. Satvaldina N. Daniyarov A. Akilzhanova A. Kairov U. Begimbetova D. Sarbassov D.D.
November 2025Multidisciplinary Digital Publishing Institute (MDPI)
International Journal of Molecular Sciences
2025#26Issue 22
Cancer cells can sustain survival independently of exogenous growth factors. To investigate their adaptation to serum deprivation, we analyzed transcriptomic responses in two cancer cell lines. Transcriptome analysis revealed upregulation of mRNAs encoding cholesterol biosynthesis enzymes. This was a critical adaptive response, as a pharmacological inhibition of the pathway with statin triggered a robust apoptotic cell death accompanied by generation of a mitochondrial reactive oxygen species. The mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cell growth, is known to be engaged in controlling lipid biosynthesis. We detected the high polysomal and preribosomal peaks not only in serum-containing medium but also under serum deprivation, indicating a high rate of protein synthesis and ribosomal biogenesis independent of serum. In addition, the inhibition of mTOR kinase activity substantially reduced polysome abundance, with a more pronounced effect in serum-deprived cancer cells. Notably, the mTOR kinase inhibition also prevented the upregulation of the cholesterol synthesis enzyme that established a direct link between mTOR activity, protein synthesis, and cholesterol biosynthesis. Together, our results show that cancer cells adapt to serum withdrawal by activating the cholesterol synthesis pathway through mTOR-dependent regulation of gene expression and protein synthesis, underscoring a critical mechanism of survival under serum withdrawal.
apoptosis , cholesterol synthesis , mechanistic target of rapamycin complex 1 (mTORC1) , polysomes , protein synthesis , reactive oxygen species , serum deprivation
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Department of Biology, School of Sciences and Humanities, Nazarbayev University, Astana, 010000, Kazakhstan
Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, 010000, Kazakhstan
Department of Biology
Center for Life Sciences
10 лет помогаем публиковать статьи Международный издатель
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