Speaker: Prof.Walter Birchmeier
Time: 2019.12.03, 12:30-13:30
Venue: Library 111 lecture hall
Wnt/β-catenin-dependent genes had previously been shown to be crucial for head and neck and intestinal carcinogenesis and the formation and maintenance of cancer stem cells. Here we identified the histone methyltransferase Mll1 as an epigenetic regulator of human and mouse head and neck and intestinal stem cells and tumors. The two systems, however, exhibited essential differences. Null mutations of Mll1 in head and neck tumor mice and in xeno-transplanted human tumors resulted in loss of self-renewal of tumor-propagating cells and in block of tumor formation, but did not alter normal tissue homeostasis. Whereas, Mll1 is highly expressed in Lgr5+ stem cells and human colon carcinomas with nuclear β-catenin. It is a prerequisite for the β-catenin-mediated expansion of stem cells in organoids and in intestinal tumors. Knockdown of Mll1 decreases the self-renewal and proliferation of colon cancer in sphere cultures and halts tumor growth in xenografts. Our results demonstrate that Mll1 is essential for Wnt/β-catenin-induced tumorigenesis and stemness in different cancers.