While cystine in parenteral nutrition has been reported to accelerate tumor growth and chemoresistance in colon cancer, its role in mediating migration and invasion in microsatellite stable (MSS)- versus microsatellite instability-high (MSI-H)-characterized colon cancer remains unclear. This study aims to investigate the effects of cystine-supplemented nutritional formulation on the migration and invasion of MSS- and MSI-H-characterized colon cancer cells. The effects of nutritional formulations containing different cystine concentrations on colon cancer cell viability, migration, and invasion were assessed through cell counting kit-8, wound healing, and transwell invasion assays. E-cadherin, Vimentin, and N-cadherin mRNA and protein levels were analyzed for evaluation of the epithelial-to-mesenchymal transition (EMT) process in tumor cells. Rapamycin was employed to analyze whether cystine-containing nutritional formulations exert their effects via the mechanistic target of rapamycin complex 1 (mTORC1) signaling. Cystine in the nutritional formulation dose-dependently increased the migration and invasion of MSI-H-characterized cancer cells, but not in MSS-characterized cancer cells. Also, cystine decreased E-cadherin and increased Vimentin and N-cadherin levels at the transcriptional and translational levels in MSI-H-characterized cancer cells, manifesting the prompting effect of cystine in the nutritional formulation on the EMT process. Moreover, cystine boosted p-p70S6K levels in MSI-H-characterized cancer cells, with no effect under Rapa treatment, indicating that cystine in the nutritional formulation works by activating the mTORC1 signaling. Cystine in nutritional formulations promotes the migration and invasion of MSI-H-characterized colon cancer cells by activating the mTORC1 signaling, providing a critical basis for optimizing nutritional support strategies for colon cancer patients.
Yan et al. (2026) studied this question.