Fig. 7: Oxaliplatin-resistant models reveal gene signatures associated with, and strategies to overcome drug resistance-induced metastasis. | Cell Death & Disease

Fig. 7: Oxaliplatin-resistant models reveal gene signatures associated with, and strategies to overcome drug resistance-induced metastasis.

From: Modeling oxaliplatin resistance in colorectal cancer reveals a SERPINE1-based gene signature (RESIST-M) and therapeutic strategies for pro-metastatic CMS4 subtype

Fig. 7

Oxaliplatin-resistant colorectal cancer (CRC) cells downregulate cholesterol biosynthesis, disrupting the localization of TGF-β receptors within caveolin-positive lipid rafts, which enhances TGF-β signaling, leading to upregulation of SERPINE1, a key driver of metastatic and invasive phenotypes in resistant CRC cells. A newly characterized SERPINE1-associated transcriptomic signature, RESIST-M, effectively stratifies CRC patients into the CMS4/iCMS3-fibrotic subtype—linked to poor prognosis, metastatic relapse, and oxaliplatin resistance. Pharmacological inhibition of PAI-1 or depletion of cellular cholesterol using statins reduces metastatic colonization and re-sensitizes resistant CRC cells to oxaliplatin. Created with BioRender.com.

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