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Cited 23 time in webofscience Cited 26 time in scopus
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Modulation of Intracellular Calcium Levels by Calcium Lactate Affects Colon Cancer Cell Motility through Calcium-Dependent Calpain

Authors
Sundaramoorthy, PasupathiSim, Jae JunJang, Yeong-SuMishra, Siddhartha KumarJeong, Keun-YeongMander, PoonamChul, Oh ByungShim, Won-SikOh, Seung HyunNam, Ky-Youb
Issue Date
28-Jan-2015
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.10, no.1
Journal Title
PLOS ONE
Volume
10
Number
1
URI
https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/10858
DOI
10.1371/journal.pone.0116984
ISSN
1932-6203
Abstract
Cancer cell motility is a key phenomenon regulating invasion and metastasis. Focal adhesion kinase (FAK) plays a major role in cellular adhesion and metastasis of various cancers. The relationship between dietary supplementation of calcium and colon cancer has been extensively investigated. However, the effect of calcium (Ca2+) supplementation on calpain-FAK-motility is not clearly understood. We sought to identify the mechanism of FAK cleavage through Ca2+ bound lactate (CaLa), its downstream signaling and role in the motility of human colon cancer cells. We found that treating HCT116 and HT-29 cells with CaLa immediately increased the intracellular Ca2+ (iCa(2+)) levels for a prolonged period of time. Ca2+ influx induced cleavage of FAK into an N-terminal FAK (FERM domain) in a dose-dependent manner. Phosphorylated FAK (p-FAK) was also cleaved in to its p-N-terminal FAK. CaLa increased colon cancer cells motility. Calpeptin, a calpain inhibitor, reversed the effects of CaLa on FAK and pFAK cleavage in both cancer cell lines. The cleaved FAK translocates into the nucleus and modulates p53 stability through MDM2-associated ubiquitination. CaLa-induced Ca2+ influx increased the motility of colon cancer cells was mediated by calpain activity through FAK and pFAK protein destabilization. In conclusion, these results suggest that careful consideration may be given in deciding dietary Ca2+ supplementation to patient undergoing treatment for metastatic cancer.
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