Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma.

MOB1, a core component of the Hippo signaling pathway, suppresses cell proliferation, and MOB1 liver conditional knockout mice develop intrahepatic cholangiocarcinoma (ICC). However, its clinical significance in human ICC has not been established. The aim of this study was to characterize protein levels and the role of Hippo and TGF pathways in ICCs. The protein levels of yes-associated protein 1 (YAP1), MOB1, Smad2, and TGFβ2 in 88 ICC cases were analyzed. Protein level was graded by a scoring system; then, the clinicopathological factors, including prognosis, were analyzed based on protein level. Nuclear overexpression of YAP1 was seen in 28 cases (31.8%), and it was significantly associated with a poor overall survival rate (p = 0.01). MOB1 expression decreased in 42 cases (47.7%) and was associated with a poor overall survival rate (p = 0.02). SMAD2 nuclear localization was significantly correlated with a high YAP1 level independent of TGFβ2. Multivariate analysis revealed that a high YAP1 level, a low MOB1 level, and lymphatic permeation were independent risk factors for overall survival. These results showed that key components of the Hippo signaling pathway are aberrantly expressed and associated with the malignant potential of human ICC.

Sugimachi K ，Nishio M ，Aishima S ，Kuroda Y ，Iguchi T ，Komatsu H ，Hirata H ，Sakimura S ，Eguchi H ，Bekki Y ，Takenaka K ，Maehara Y ，Suzuki A ，Mimori K ... -  《-》

Dysregulated YAP1/TAZ and TGF-β signaling mediate hepatocarcinogenesis in Mob1a/1b-deficient mice.

Nishio M ，Sugimachi K ，Goto H ，Wang J ，Morikawa T ，Miyachi Y ，Takano Y ，Hikasa H ，Itoh T ，Suzuki SO ，Kurihara H ，Aishima S ，Leask A ，Sasaki T ，Nakano T ，Nishina H ，Nishikawa Y ，Sekido Y ，Nakao K ，Shin-Ya K ，Mimori K ，Suzuki A ... -  《-》

Up-regulation of 14-3-3ζ expression in intrahepatic cholangiocarcinoma and its clinical implications.

Zhang C ，Liu LX ，Dong ZR ，Shi GM ，Cai JB ，Zhang PF ，Ke AW ，Yu JX ，Zhou J ，Fan J ... -  《-》

Autocrine parathyroid hormone-like hormone promotes intrahepatic cholangiocarcinoma cell proliferation via increased ERK/JNK-ATF2-cyclinD1 signaling.

Tang J ，Liao Y ，He S ，Shi J ，Peng L ，Xu X ，Xie F ，Diao N ，Huang J ，Xie Q ，Lin C ，Luo X ，Liao K ，Ma J ，Li J ，Zhou D ，Li Z ，Xu J ，Zhong C ，Wang G ，Bai L ... -  《Journal of Translational Medicine》

Loss of FoxA2 accelerates neoplastic changes in the intrahepatic bile duct partly via the MAPK signaling pathway.

Shen J ，Zhou Y ，Zhang X ，Peng W ，Peng C ，Zhou Q ，Li C ，Wen T ，Shi Y ... -  《Aging-US》