title: Decreased TIP30 promotes Snail-mediated epithelial-mesenchymal transition and tumor-initiating properties in hepatocellular carcinoma.
abstract: The poor prognosis of hepatocellular carcinoma (HCC) is mainly due to tumor recurrence and metastases. Recently, epithelial-mesenchymal transition (EMT) has been implicated in tumor invasion and metastasis. However, the underlying molecular mechanisms are yet to be elucidated. Here, we show that 30-kDa Tat-interacting protein (TIP30), also called CC3, is significantly downregulated during transforming growth factor-β-induced EMT. In our in vitro and in vivo studies, we show that decreased TIP30 expression leads to EMT, as well as enhanced motility and invasion of HCC cells. Also, increased self-renewal ability and chemotherapeutic resistance are observed with TIP30 depletion. Moreover, Snail is one of the key transcription factors promoting EMT, and overexpression of TIP30 greatly decreased nucleic accumulation in Snail through the regulation of intracellular localization. Small interfering RNAs targeting Snail attenuated EMT and tumor-initiating properties induced by TIP30 deficiency. We further confirmed that TIP30 competitively interrupted the interaction of Snail with importin-β2 to block the nuclear import of Snail. Consistently, TIP30 expression significantly correlates with E-cadherin expression in HCC patients. TIP30 or combination of E-cadherin is a powerful marker in predicting the prognosis of HCC. Taken together, our results suggest a novel and critical role of TIP30 involved in HCC progression and aggressiveness.
authors.affiliation: 1] International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China [2] Changhai Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Zhu
authors.affiliation: 1] International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China [2] PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, Beijing, People's Republic of China.
authors.forename: F
authors.initials: F
authors.lastname: Yin
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.affiliation: Changhai Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Jing
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.affiliation: Changhai Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: F
authors.initials: F
authors.lastname: Bu
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Tong
authors.affiliation: Changhai Hospital, The Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.affiliation: 1] International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China [2] PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, Beijing, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: 1] International Joint Cancer Research Institute, The Second Military Medical University, Shanghai, People's Republic of China [2] PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, Beijing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000123:Acetyltransferases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D028961:beta Karyopherins / Q000378:metabolism
chemical_list: D015820:Cadherins; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; C108121:TNPO1 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D028961:beta Karyopherins; D000123:Acetyltransferases; C111246:HTATIP2 protein, human