In the course of our study, we confirmed that MATα2 is secreted and uncovered two new aspects of MATα2 biology: first, that EV-MATα2 can be internalized and translocate to the nucleus to act as a transcription factor, and second, a previously unreported truncated form of MATα2 (MATα2-t) is preferentially released by cancer cells and is essential for cancer cell survival in part by activating FAK. Here, MAT2A is linked to cancer.