Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899913 | Cancer Letters | 2013 | 9 Pages |
Abstract
Intracellular free calcium is a ubiquitous second messenger regulating a multitude of normal and pathogenic cellular responses, including the development of melanoma. Upstream signaling pathways regulating the intracellular free calcium concentration ([Ca2+]i) may therefore have a significant impact on melanoma growth and metastasis. In this study, we demonstrate that the endoplasmic reticulum (ER)-associated protein calcium-modulating cyclophilin ligand (CAML) is bound to Basigin, a widely expressed integral plasma membrane glycoprotein and extracellular matrix metalloproteinase inducer (EMMPRIN, or CD147) implicated in melanoma proliferation, invasiveness, and metastasis. This interaction between CAML and Basigin was first identified using yeast two-hybrid screening and further confirmed by co-immunoprecipitation. In human A375 melanoma cells, CAML and Basigin were co-localized to the ER. Knockdown of Basigin in melanoma cells by siRNA significantly decreased resting [Ca2+]i and the [Ca2+]i increase induced by the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) inhibitor thapsigargin (TG), indicating that the interaction between CAML and Basigin regulates ER-dependent [Ca2+]i signaling. Meanwhile upregulating the [Ca2+]i either by TG or phorbol myristate acetate (PMA) could stimulate the production of MMP-9 in A375 cells with the expression of Basigin. Our study has revealed a previously uncharacterized [Ca2+]i signaling pathway that may control melanoma invasion, and metastasis. Disruption of this pathway may be a novel therapeutic strategy for melanoma treatment.
Keywords
ThapsigarginmIgGTACIWCLMMPNF-ATEMMPRINCAMLortho-nitrophenyl-β-d-galactopyranosideIgGsi-RNAMouse IgGPMASmall interfering RNAextracellular matrix metalloproteinase inducerimmunoglobulin BasiginMelanomasarco/endoplasmic reticulum Ca2+-ATPaseCo-IPfull lengthphorbol myristate acetateSERCAwhole cell lysatematrix metalloproteinaseCo-ImmunoprecipitationCalcium
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Authors
Tingting Long, Juan Su, Wen Tang, Zhongling Luo, Shuang Liu, Zhaoqian Liu, Honghao Zhou, Min Qi, Weiqi Zeng, Jianglin Zhang, Xiang Chen,