Extracellular Vesicles Derived-LAT1 mRNA as a Powerful Inducer of Colorectal Cancer Aggressive Phenotype

SIMPLE SUMMARY: The metastatic spread of tumor cells to the liver is one of the most common causes of mortality in CRC. Extracellular vesicles are currently considered vehicles of metastization, playing a role in the modification of the recipient cell’s phenotype. LAT1 and ASCT2 are amino acids transporters associated with increased proliferation in CRC. This study analyzed the effect of LAT1 and ASCT2 mRNAs derived from CRC-EVs in the phenotype modulation of recipient cells. In this study we demonstrate LAT1-EVs mRNA involvement in recipient cells’ phenotype modulation, conferring advantages in cell migration and proliferation. ABSTRACT: Colorectal cancer (CRC) is the third most common cancer in the world and represents the third most deadly tumor worldwide. About 15–25% of patients present metastasis in the moment of diagnosis, the liver being the most common site of metastization. Therefore, the development of new therapeutic agents is needed, to improve the patients’ prognosis. Amino acids transporters, LAT1 and ASCT2, are described as upregulated in CRC, being associated with a poor prognosis. Extracellular vesicles have emerged as key players in cell-to-cell communication due to their ability to transfer biomolecules between cells, with a phenotypic impact on the recipient cells. Thus, this study analyzes the presence of LAT1 and ASCT2 mRNAs in CRC-EVs and evaluates their role in phenotype modulation in a panel of four recipient cell lines (HCA-7, HEPG-2, SK-HEP-1, HKC-8). We found that HCT 116-EVs carry LAT1, ASCT2 and other oncogenic mRNAs being taken up by recipient cells. Moreover, the HCT 116-EVs’ internalization was associated with the increase of LAT1 mRNA in SK-HEP-1 cells. We also observed that HCT 116-EVs induce a higher cell migration capacity and proliferation of SK-HEP-1 and HKC-8 cells. The present study supports the LAT1-EVs’ mRNA involvement in cell phenotype modulation, conferring advantages in cell migration and proliferation.