Quantitative proteomics identifies myoferlin as a novel regulator of A Disintegrin and Metalloproteinase 12 in HeLa cells

It has been found that A Disintergrin And Metalloproteinase 12 (ADAM12) is significantly higher in multiple tumors and it has been used as a prognostic marker for cancer progression. Several ADAM12 substrates have been identified biochemically and the role of -its proteolytic function has been explored. However, its non-proteolytic function and its interacting partners have not been systematically studied. In this work, we used a MS-based quantitative proteomic approach to identify the interacting partners of the full length ADAM12 in a cervical cancer cell line. ThroughAfter bioinformatic analyses and biochemical experiments, we found that ADAM12 could regulate its interacting partners through its non-enzymatic function, such as leading to the enhanced expression of vimentin, a mesenchymal marker. In addition, the stability of ADAM12 itself was enhanced by myoferlin, which regulates cancer cell proliferation and invasion. Together, with previous findings, ADAM12 may be an intermediate molecule that links the high expression of myoferlin and vimentin in cancer progression. This result may reveal the potential non-proteolytic function of ADAM12 in cancer cellularcell biology. The information obtained here may be used to develop new strategies to alter the signaling pathways involving the non-catalytic function of ADAM12.