Disruption of tumor cell adhesion promotes angiogenic switch and progression to micrometastasis in RAF-Driven murine lung cancer

作者：Ceteci Fatih; Ceteci Semra; Karreman Christiaan; Kramer Boris W; Asan Esther; Goetz Rudolf; Rapp Ulf R

来源：Cancer Cell, 2007, 12(2): 145-159.

DOI：10.1016/j.ccr.2007.06.014

Progression of non-small-cell lung cancer (NSCLC) to metastasis is poorly understood. Two genetic approaches were used to evaluate the role of adherens junctions in a C-RAF driven mouse model for NSCLC: conditional ablation of the cdh1 gene and expression of dominant-negative (dn) E-cadherin. Disruption of E-cadherin caused massive formation of intratumoral vessels that was reversible in the early phase of induction. Vascularized tumors grew more rapidly, developed invasive fronts, and gave rise to micrometastasis. beta-catenin was identified as a critical effector of E-cadherin disruption leading to upregulation of VEGF-A and VEGF-C. In vivo, lung tumor cells with disrupted E-cadherin expressed beta-catenin target genes normally found in other endodermal lineages suggesting that reprogramming may be involved in metastatic progression.

• 出版日期2007-8
• 单位河北医科大学