CALCIUM AT THE PUMP: REGULATION OF INTRACELLULAR CALCIUM BY SECRETORY PATHWAY CALCIUM ATPASE ISOFORM 2 (SPCA2) IN MODELS OF LACTATION AND BREAST CANCER
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Date
2013-09-06
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Johns Hopkins University
Abstract
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.
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Keywords
SPCA2, breast cancer, Orai1, calcium, lactation