title: Contribution of TIP30 to chemoresistance in laryngeal carcinoma.
abstract: Laryngeal squamous cell carcinoma (LSCC) is one of the most common carcinomas of the head and neck. Despite advances in diagnosis and treatment, the survival of patients with LSCC has not improved in the past two decades. TIP30, a newly identified tumour suppressor, appears to be involved in multiple processes during tumour development. Here, we investigated the involvement of TIP30 in chemoresistance of LSCC in vitro and in vivo. We showed that TIP30 expression decreased significantly in drug-selected cells (DSCs) of laryngeal carcinoma. Suppressing TIP30 enhanced resistance capability to multiple chemotherapy drugs, cell proliferation and self-renewal in Hep2 cells. Additionally, decreased self-renewal capacity and chemotherapeutic resistance were observed in DSCs overexpressing TIP30. Furthermore, TIP30 negatively regulated tumourigenesis and chemoresistance in LSCC cells subcutaneously transplanted into nude mice. Moreover, decreased TIP30 expression contributed to chemoresistance, self-renewal and proliferation of LSCC cells via nuclearlisation of β-catenin, a cell-cell adhesion and stem cell renewal regulator. Consistently, Kaplan-Meier and Cox proportional hazards regression modelling analyses showed that decreased TIP30 expression independently predicted poor survival in patients with LSCC. Taken together, our results reveal that TIP30 has a crucial role in chemoresistance of LSCC through the AKT/glycogen synthase kinase-3β/β-catenin signalling pathway and may be a promising candidate for improving LSCC chemotherapy.
authors.affiliation: 1] International Joint Cancer Research Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China [2] Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, 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, 800 Xiangyin Road, Shanghai 200433, People's Republic of China [2] PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing, People's Republic of China.
authors.forename: F
authors.initials: F
authors.lastname: Yin
authors.affiliation: Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: R
authors.initials: R
authors.lastname: Chen
authors.affiliation: Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, 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, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Fan
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: R
authors.initials: R
authors.lastname: Jia
authors.affiliation: International Joint Cancer Research Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, 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, 800 Xiangyin Road, Shanghai 200433, People's Republic of China [2] PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, 28 Fuxing Road, 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, 800 Xiangyin Road, Shanghai 200433, People's Republic of China [2] PLA General Hospital Cancer Center, PLA Postgraduate School of Medicine, 28 Fuxing Road, Beijing, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000368:Aged; D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D051176:beta Catenin; D000123:Acetyltransferases; C111246:HTATIP2 protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3