Orai1 and STIM1 are critical for breast tumor cell migration and metastasis.
Tumor metastasis is the primary cause of death of cancer patients. Understanding the molecular mechanisms underlying tumor metastasis will provide potential drug targets. We report here that Orai1 and STIM1, both of which are involved in store-operated calcium entry, are essential for breast tumor cell migration in vitro and tumor metastasis in mice. Reduction of Orai1 or STIM1 by RNA interference in highly metastatic human breast cancer cells or treatment with a pharmacological inhibitor of store-operated calcium channels decreased tumor metastasis in animal models. Our data demonstrate a role for Orai1 and STIM1 in tumor metastasis and suggest store-operated calcium entry channels as potential cancer therapeutic targets.
Yang
Shengyu
S
Department of Physiology, Weill Medical College of Cornell University, New York, NY 10065, USA.
Zhang
J Jillian
JJ
Huang
Xin-Yun
XY
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000473:pathology / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D000071740:ORAI1 Protein; D034622:RNA Interference; D000071737:Stromal Interaction Molecule 1; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007093:Imidazoles; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C520430:Orai1 protein, mouse; C103530:STIM1 protein, human; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D020703:ras GTPase-Activating Proteins; D020744:rac GTP-Binding Proteins; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium