Altered Expression of Hippo Signaling Pathway Molecules in Intrahepatic Cholangiocarcinoma

Keishi Sugimachi, Miki Nishio, Shinichi Aishima, Yohsuke Kuroda, Tomohiro Iguchi, Hisateru Komatsu, Hidenari Hirata, Shotaro Sakimura, Hidetoshi Eguchi, Yuki Bekki, Kenji Takenaka, Yoshihiko Maehara, Akira Suzuki, Koshi Mimori

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Objective: 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. Methods: 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. Results: 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. Conclusions: These results showed that key components of the Hippo signaling pathway are aberrantly expressed and associated with the malignant potential of human ICC.

Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalOncology (Switzerland)
Issue number1
Publication statusPublished - Jul 1 2017

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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