RT info:eu-repo/semantics/article
T1 A reciprocal shift in transient receptor potential channel 1 (TRPC1) and stromal interaction molecule 2 (STIM2) contributes to Ca2+remodeling and cancer hallmarks in colorectal carcinoma cells
A1 Sobradillo Luengo, Diego
A1 Hernández Morales, Miriam
A1 Ubierna, Daniel
A1 Moyer, Mary P.
A1 Núñez Llorente, Lucía
A1 Villalobos Jorge, Carlos
K1 Colorectal cancer
K1 Cáncer colorrectal
K1 Calcium
K1 Calcio
AB We have investigated the molecular basis of intracellular Ca2+ handling in human colon carcinoma cells (HT29) versus normal human mucosa cells (NCM460) and its contribution to cancer features. We found that Ca2+ stores in colon carcinoma cells are partially depleted relative to normal cells. However, resting Ca2+ levels, agonist-induced Ca2+ increases, store-operated Ca2+ entry (SOCE), and store-operated currents (ISOC) are largely enhanced in tumor cells. Enhanced SOCE and depleted Ca2+ stores correlate with increased cell proliferation, invasion, and survival characteristic of tumor cells. Normal mucosa cells displayed small, inward Ca2+ release-activated Ca2+ currents (ICRAC) mediated by ORAI1. In contrast, colon carcinoma cells showed mixed currents composed of enhanced ICRAC plus a nonselective ISOC mediated by TRPC1. Tumor cells display increased expression of TRPC1, ORAI1, ORAI2, ORAI3, and STIM1. In contrast, STIM2 protein was nearly depleted in tumor cells. Silencing data suggest that enhanced ORAI1 and TRPC1 contribute to enhanced SOCE and differential store-operated currents in tumor cells, whereas ORAI2 and -3 are seemingly less important. In addition, STIM2 knockdown decreases SOCE and Ca2+ store content in normal cells while promoting apoptosis resistance. These data suggest that loss of STIM2 may underlie Ca2+ store depletion and apoptosis resistance in tumor cells. We conclude that a reciprocal shift in TRPC1 and STIM2 contributes to Ca2+ remodeling and tumor features in colon cancer.
PB Elsevier
SN 0021-9258
YR 2014
FD 2014
LK http://uvadoc.uva.es/handle/10324/45054
UL http://uvadoc.uva.es/handle/10324/45054
LA eng
NO Journal of Biological Chemistry, 2014, vol. 289, n. 42. p. 28765-28782
NO Producción Científica
DS UVaDOC
RD 20-may-2024