YAP-associated chromosomal instability and cholangiocarcinoma in mice.

YAP-associated chromosomal instability and cholangiocarcinoma in mice. Oncotarget. 2018 Jan 19;9(5):5892-5905 Authors: Rizvi S, Fischbach SR, Bronk SF, Hirsova P, Krishnan A, Dhanasekaran R, Smadbeck JB, Smoot RL, Vasmatzis G, Gores GJ Abstract Deregulated Hippo pathway signaling is associated with aberrant activation of the downstream effector yes-associated protein (YAP), an emerging key oncogenic mediator in cholangiocarcinoma (CCA). In our prior work, we have demonstrated that biliary transduction of YAP along with Akt as a permissive factor induces CCA in mice. To further delineate the mechanisms associated with YAP-associated biliary oncogenesis, we have established seven malignant murine cell lines from our YAP-driven murine CCA model. These cells express the CCA markers SRY (Sex Determining Region Y)-Box 9 (SOX9), cytokeratin (CK)-7 and 19 but lack hepatocyte nuclear factor 4 alpha and alpha-smooth muscle actin, markers of hepatocellular carcinoma and cancer-associated fibroblasts, respectively. Notably, the murine CCA cells can be readily implanted into mouse livers with resultant orthotopic tumor formation. In this unique syngeneic orthotopic murine model, tumors exhibit histopathologic features resembling human CCA. We analyzed transcriptome data from YAP-associated parent CCA tumor nodules and identified a gene expression pattern associated with chromosomal instability, known as CIN25. Similarly, mate-pair sequencing of t...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research