Cancer Cell重大发现 维生素A治疗结肠癌   癌症研究

Cancer Cell重大发现 维生素A治疗结肠癌 癌症研究

时间:2020-02-12 15:25 作者:admin 点击:
阅读模式 HOXA5 Counteracts Stem Cell Traits by Inhibiting Wnt Signaling in Colorectal Cancer Paloma Ordó?ez-Morán1, Caroline Dafflon1, Masamichi Imajo2, 3, 4, Eisuke Nishida3, 4, Joerg Huelsken Hierarchical organization of tissues relies on stem cells, which either self-renew or produce committed progenitors predestined for lineage differentiation. Here we identify HOXA5 as an important repressor of intestinal stem cell fate in vivo and identify a reciprocal feedback between HOXA5 and Wnt signaling. HOXA5 is suppressed by the Wnt pathway to maintain stemness and becomes active only outside the intestinal crypt where it inhibits Wnt signaling to enforce differentiation. In colon cancer, HOXA5 is downregulated, and its re-expression induces loss of the cancer stem cell phenotype, preventing tumor progression and metastasis. Tumor regression by HOXA5 induction can be triggered by retinoids, which represent tangible means to treat colon cancer by eliminating cancer stem cells.