Abstract B41: EMC1 influences cellular calcium homeostasis and promotes breast cancer cell migration and proliferation

Abstract

Abstract Endoplasmic Reticulum Membrane Complex protein 1 (EMC1), also named KIAA0090, was recently identified as part of a complex with six proteins (EMC1-EMC6) proposed to participate in the folding/maturation of membrane proteins, but the mechanisms remains unclear. High throughput studies reveal that EMC1 gene is up-regulated in many types of cancer and up-regulation correlates to poor survival rates. It has been known that there is a close relationship between proteins involved in the unfolded protein response (UPR) and tumor maintenance. Here, we investigated the involvement of EMC1 in breast cancer cell proliferation and migration. We showed by qPCR that EMC1 gene is overexpressed in breast cancer cell lines in comparison to immortalized epithelial breast cells. Next, we stably overexpressed EMC1 in MCF-7 and SKBR-3 cell lines. Overexpression led to an increase in proliferation rates, clonogenic capacity, and migration in wound-healing assays. Consistently, EMC1 knockdown in SKBR-3 cells led to a decrease of cell migration and clonogenic capacity. Furthermore, we assessed by Fluo3 the involvement of EMC1 in the regulation of intracellular calcium levels in SKBR-3 cells in response to thapsigargin treatment, which inhibits the endoplasmic reticulum Ca2+ ATPase. SKBR-3 control cells showed an expected increment in cytosolic calcium levels following thapsigargin addition. Interestingly, cytosolic calcium increments were about 50% higher in EMC1 overexpressing cells and nearly 10-fold lower in knockdown cells, suggesting a role for EMC1 in the control of cellular calcium homeostasis. EMC1 could function in the maturation/assembly of calcium channels or calcium pumps, thereby promoting breast cancer cell migration and maintenance. Citation Format: Roberto Augusto Silva Molina, Rodrigo Ribeiro Silva, Roberta Ribeiro Costa, Silmara Reis Banzi, Enilza Maria Espreafico. EMC1 influences cellular calcium homeostasis and promotes breast cancer cell migration and proliferation. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B41.