On The Role of Myelin and Lymphocyte Protein (MAL) In Cancer: A Puzzle With Two Faces

Myelin and lymphocyte protein (MAL) is an integral membrane protein constituent of lipid rafts, and it is implicated in apical transport of proteins in polarized epithelial cells. However, beyond the involvement of MAL in apical sorting and as its function as a raft stabilizer, it is still not totally clear how MAL participates in cell proliferating processes. More controversial and interesting is the fact that MAL has been implicated in carcinogenesis in two opposite ways. First, this protein is overexpressed in ovarian cancer and some kinds of lymphomas where it seems to favor cancer progression. Conversely, it has been reported that downregulation of the MAL gene by promoter hypermethylation is a hallmark of several adenocarcinomas. So far, there is not enough experimental evidence to help us understand this phenomenon, and no MAL mutations or MAL isoforms have been associated with these opposite functions. This review provides an updated summary of the structure and functions of MAL, and we will discuss the possible mechanisms underlying its roles as a tumor suppressor and a tumor progression factor.