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MS4A12 Is a Colon-Selective Store-Operated Calcium Channel Promoting Malignant Cell Processes

¹ Department of Internal Medicine III, Division of Experimental and Translational Oncology, Johannes Gutenberg University; ² Ganymed Pharmaceuticals AG, Mainz, Germany; and ³ Institute of Pathology, Algemeen Stedelijk Ziekenhuis, Aalst, Belgium

Requests for reprints: Özlem Türeci, Ganymed Pharmaceuticals AG, Freiligrathstr. 12, 55131 Mainz, Germany. Phone: 49-6131-1440100; Fax: 49-6131-1440111; E-mail: oe.tuereci{at}ganymed-pharmaceuticals.com.

Key Words: antibody target • calcium channel • colon cancer

Using a data mining approach for the discovery of new targets for antibody therapy of colon cancer, we identified MS4A12, a sequence homologue of CD20. We show that MS4A12 is a cell surface protein. Expression analysis and immunohistochemistry revealed MS4A12 to be a colonic epithelial cell lineage gene confined to the apical membrane of colonocytes with strict transcriptional repression in all other normal tissue types. Expression is maintained upon malignant transformation in 63% of colon cancers. Ca²⁺ flux analyses disclosed that MS4A12 is a novel component of store-operated Ca²⁺ entry in intestinal cells. Using RNAi-mediated gene silencing, we show that loss of MS4A12 in LoVo colon cancer cells attenuates epidermal growth factor receptor–mediated effects. In particular, proliferation, cell motility, and chemotactic invasion of cells are significantly impaired. Cancer cells expressing MS4A12, in contrast, are sensitized and respond to lower concentrations of epidermal growth factor. In summary, these findings have implications for both the physiology of colonic epithelium as well as for the biology and treatment of colon cancer. [Cancer Res 2008;68(9):3458–66]

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				Correction: MS4A12 in Colon Cancer Cancer Res., June 15, 2008; 68(12): 4958 - 4958. [Full Text] [PDF]