Protein arginine methylation is catalyzed by
protein arginine methyltransferases (PRMTs) and plays an important role in many cellular processes. Aberrant PRMT expression has been observed in several common
cancer types; however, their precise contribution to the cell transformation process is not well understood. We previously reported that the PRMT1 gene generates several alternatively spliced
isoforms, and our initial biochemical characterization of these
isoforms revealed that they exhibit distinct substrate specificity and subcellular localization. We focus here on the PRMT1v2
isoform, which is the only predominantly cytoplasmic
isoform, and we have found that its relative expression is increased in
breast cancer cell lines and
tumors. Specific depletion of PRMT1v2 using RNA interference caused a significant decrease in
cancer cell survival due to an induction of apoptosis. Furthermore, depletion of PRMT1v2 in an aggressive
cancer cell line significantly decreased cell invasion. We also demonstrate that PRMT1v2 overexpression in a non-aggressive
cancer cell line was sufficient to render them more invasive. Importantly, this novel activity is specific to PRMT1v2, as overexpression of other
isoforms did not enhance invasion. Moreover, this activity requires both proper subcellular localization and methylase activity. Lastly, PRMT1v2 overexpression altered cell morphology and reduced cell-cell adhesion, a phenomenon that we convincingly linked with reduced β-
catenin protein expression. Overall, we demonstrate a specific role for PRMT1v2 in
breast cancer cell survival and invasion, underscoring the importance of identifying and characterizing the distinct functional differences between PRMT1
isoforms.