CALCIUM AT THE PUMP: REGULATION OF INTRACELLULAR CALCIUM BY SECRETORY PATHWAY CALCIUM ATPASE ISOFORM 2 (SPCA2) IN MODELS OF LACTATION AND BREAST CANCER
Johns Hopkins University
Secretory Pathways Calcium ATPase 2 (SPCA2) is a non-redundant isoform of SPCA expressed in highly secretory cells. In this study we aimed to investigate physiological regulation of SPCA2 as a possible regulator of calcium during lactation and its interaction with the canonical, store-dependent calcium channel, Orai1. Furthermore, we asked if there were other calcium channels which showed positive interactions with SPCA2. We found that TRPC6 also interacts with SPCA2 during lactation, but is, however reciprocally regulated by SPCA2 expression. Ultimately, we learned that differential regulation of calcium transporters we entitled CALTRANS, had specific expression patterns in the progression of cancer, as well. Furthermore, we show explicit calcium signaling modes for a tumorigenic and metastatic cell model of cancer. The addition of SPCA2 to a migratory cell line showed promise in increasing adhesion, while overexpression of SPCA2 in a tumorigenic cell model was attenuated with natural phytochemicals.
SPCA2, breast cancer, Orai1, calcium, lactation