An investigation of tropomyosin 4 in the regulation of invadopodia and motility in MDA-MB-231

Abstract

Tropomyosins are α-helical coiled coil proteins that bind actin filaments. Four genes encode the tropomyosin family of proteins that includes about 40 members. Studies of tropomyosins revealed a functional diversity between different isoforms. TPM4 gene encodes 2 isoforms: tropomyosin 4 low molecular weight (TM4 LMW) and tropomyosin 4 high molecular weight (TM4 HMW). TM4 LMW has been reported to regulate resorptive capacity of osteoclasts. However, the role of TM4 in facilitating degradation and motility in cancer cells has not been investigated yet. In this research, I used siRNAs to TM4 LMW and TM4 HMW and performed degradation and migration assays in MDA-MB-231 breast cancer cells to study the role of both isoforms. I found that degradation is regulated by TM4 LMW, but not TM4 HMW. This is first evidence that TM4 might regulate invadopodia dynamics in tumor cells. In addition, this result might indicate that TM4 isoforms don’t possess a redundant function. Further research should focus on mechanism underlying the observed effect by TM4 LMW. In conclusion, this study contributes to our knowledge regarding invadopodia and the role of cytoskeletal proteins in the regulation of these structures.