COMMD1 disrupts HIF-1a/b dimerization and inhibits human tumor cell invasion (J Clin Invest, 2010, 120:2119-2130)

報告日期: 2011/03/18
報告時間: 16:00/16:50
報告學生: 許晉源 (英文報告)
講評老師: 張文粲

Full Text:

COMMD1 disrupts HIF-1alpha/beta dimerization and inhibits human tumor cell invasion
van de Sluis B, Mao X, Zhai Y, Groot AJ, Vermeulen JF, van der Wall E, van Diest PJ, Hofker MH, Wijmenga C, Klomp LW, Cho KR, Fearon ER, Vooijs M, Burstein E.
J Clin Invest. 120, 2119-2130 (2010)

Commentator:張文粲 老師
Time: 2011/03/18 16:00 - 16:50
Place:Room 602

COMM domain–containing 1 (COMMD1) is the prototype protein family belongs to the copper metabolism gene MURR1 domain (COMMD) family. COMMD1 protein has been shown to regulate of copper and sodium transport, cell cycle progression, and both HIF- and NF-κB-mediated gene expression. HIF and NF-κB are transcription factors that promote cancer cell growth, survival, and invasion. In this study, authors clarified the role of COMMD1 in both HIF- and NF-κB-mediated tumor invasion suggested that the COMMD1 may be inactivated or repressed in tumors. They reported that COMMD1 expression is suppressed in many types of human cancer and that decreased COMMD1 expression is correlated with malignancy in human cancer. In a chick xenograft model showed that suppressed COMMD1 expression led to increased tumor invasion in human cell lines. Increased COMMD1 expression results in decreasing lung metastasis in a mouse model. Decreased COMMD1 expression is also related to increased HIF and other genes expression known to promote cancer cell invasion. Finally, they demonstrated that COMMD1 binds to the amino terminus of HIF-1α to inhibit HIF-mediated gene expression and prevent HIF-1α/HIF-1β formation, and then disrupt DNA binding and transcriptional activation. This study demonstrates that COMMD1 inhibits human cancer invasion and provides new insights into the mechanism involved in regulation of HIF pathway in cancer cells.

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