MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis (Nat Med, 2009, 15:59-67)

報告日期: 2009/04/10
報告時間: 15:10/16:00
報告學生: 溫凡志
講評老師: 周楠華

MACC1, a newly identified key regulator of HGF-MET signaling, predicts colon cancer metastasis


Ulrike Stein, Wolfgang Walther, Franziska Arlt, Holger Schwabe, Janice Smith, Iduna Fichtner, Walter Birchmeier & Peter M Schlag

Nature Medicine. 15, 59 - 67 (2008)


Speaker: 溫凡志

Commentator: 周楠華老師

Time / Date: 15:10-16:00, April 10, 2009

Room: 602



     MACC1, a novel prognostic marker for metastasis in colon cancer, was identified by differential display RT-PCR in specimens. Simultaneously overexpression of MET, a hepatocyte growth factor (HGF) receptor, was detected and highly correlated with the expression level of MACC1. Ectopic expression of MACC1 but not MACC1 SH3 and PXXP mutants in colon cancer cells induced MET mRNA expression and increased cell migration and invasion capacities. Cell scattering and proliferation induced by HGF was unique in expressing MACC1 cells and was blocked under MACC1 or MET siRNA treatment, besides, HGF led to the translocation of MACC1 form cytoplasm to nucleus. By EMSA and ChIP assay, MACC1 was demonstrated that bound directly to the promoter region of MET to activate its expression. In mice model, orthotopic transplantation of cancer cells expressing MACC1 strongly increased the tumor volume and promoted liver metastasis but was reversed these changes by MACC1 or MET shRNA. Briefly, the newly identified regulator, MACC1, may be used as a therapeutic target to be interfered to prevent patients from metastasis formation and raised metastasis-free survival rates in clinics.



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