PMID- 23879967 OWN - NLM STAT- MEDLINE DCOM- 20131030 LR - 20171116 IS - 1872-7980 (Electronic) IS - 0304-3835 (Linking) VI - 339 IP - 1 DP - 2013 Oct 1 TI - A novel interaction between calcium-modulating cyclophilin ligand and Basigin regulates calcium signaling and matrix metalloproteinase activities in human melanoma cells. PG - 93-101 LID - S0304-3835(13)00539-9 [pii] LID - 10.1016/j.canlet.2013.07.019 [doi] AB - 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 Ca(2+)-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. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Long, Tingting AU - Long T AD - Department of Dermatology, XiangYa Hospital, Central South University, Changsha, Hunan, China. FAU - Su, Juan AU - Su J FAU - Tang, Wen AU - Tang W FAU - Luo, Zhongling AU - Luo Z FAU - Liu, Shuang AU - Liu S FAU - Liu, Zhaoqian AU - Liu Z FAU - Zhou, Honghao AU - Zhou H FAU - Qi, Min AU - Qi M FAU - Zeng, Weiqi AU - Zeng W FAU - Zhang, Jianglin AU - Zhang J FAU - Chen, Xiang AU - Chen X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130720 PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (CAMLG protein, human) RN - 136894-56-9 (Basigin) RN - EC 3.4.24.- (Matrix Metalloproteinases) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - SY7Q814VUP (Calcium) SB - IM MH - Adaptor Proteins, Signal Transducing/chemistry/*metabolism MH - Basigin/chemistry/genetics/*metabolism MH - Calcium/metabolism MH - *Calcium Signaling MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Intracellular Space/metabolism MH - Matrix Metalloproteinase 9/genetics/metabolism MH - Matrix Metalloproteinases/*metabolism MH - Melanoma/genetics/*metabolism MH - Protein Binding MH - Protein Interaction Domains and Motifs MH - Protein Transport OTO - NOTNLM OT - Basigin OT - CAML OT - Calcium OT - D105-199 OT - D207-230 OT - D207-269 OT - D231-269 OT - D34-89 OT - EMMPRIN OT - FL OT - IgG OT - MMP OT - Melanoma OT - NF-AT OT - OPNG OT - PMA OT - SERCA OT - TACI OT - TG OT - WCL OT - calcium modulating cyclophilin ligand OT - co-IP OT - co-immunoprecipitation OT - deletion of the cytoplasmic domain OT - deletion of the first IgG OT - deletion of the second IgG OT - deletion of the transmembrane and cytoplasmic domain OT - deletion of the transmembrane domain OT - extracellular matrix metalloproteinase inducer OT - full length OT - immunoglobulin OT - mIgG OT - matrix metalloproteinase OT - mouse IgG OT - ortho-nitrophenyl-beta-D-galactopyranoside OT - phorbol myristate acetate OT - sarco/endoplasmic reticulum Ca(2+)-ATPase OT - si-RNA OT - small interfering RNA OT - thapsigargin OT - the nuclear factor of activated T cells transcription factor OT - transmembrane activator and CAML-interactor OT - whole cell lysate EDAT- 2013/07/25 06:00 MHDA- 2013/10/31 06:00 CRDT- 2013/07/25 06:00 PHST- 2013/05/08 00:00 [received] PHST- 2013/07/11 00:00 [revised] PHST- 2013/07/15 00:00 [accepted] PHST- 2013/07/25 06:00 [entrez] PHST- 2013/07/25 06:00 [pubmed] PHST- 2013/10/31 06:00 [medline] AID - S0304-3835(13)00539-9 [pii] AID - 10.1016/j.canlet.2013.07.019 [doi] PST - ppublish SO - Cancer Lett. 2013 Oct 1;339(1):93-101. doi: 10.1016/j.canlet.2013.07.019. Epub 2013 Jul 20.