PMID- 25321475 OWN - NLM STAT- MEDLINE DCOM- 20150618 LR - 20211021 IS - 2041-4889 (Electronic) VI - 5 IP - 10 DP - 2014 Oct 16 TI - Contribution of TIP30 to chemoresistance in laryngeal carcinoma. PG - e1468 LID - 10.1038/cddis.2014.424 [doi] AB - 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 beta-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-3beta/beta-catenin signalling pathway and may be a promising candidate for improving LSCC chemotherapy. FAU - Zhu, M AU - Zhu M AD - 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. FAU - Yin, F AU - Yin F AD - 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. FAU - Yang, L AU - Yang L AD - Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - Chen, S AU - Chen S AD - Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - Chen, R AU - Chen R AD - International Joint Cancer Research Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - Zhou, X AU - Zhou X AD - Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - Jing, W AU - Jing W AD - Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - Fan, X AU - Fan X AD - International Joint Cancer Research Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - Jia, R AU - Jia R AD - International Joint Cancer Research Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - Wang, H AU - Wang H AD - International Joint Cancer Research Institute, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - Zheng, H AU - Zheng H AD - Changhai Hospital, The Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China. FAU - Zhao, J AU - Zhao J AD - 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. FAU - Guo, Y AU - Guo Y AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141016 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Transcription Factors) RN - 0 (beta Catenin) RN - EC 2.3.1.- (Acetyltransferases) RN - EC 2.3.1.48 (HTATIP2 protein, human) RN - EC 2.7.11.1 (GSK3B protein, human) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (Gsk3b protein, mouse) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) SB - IM MH - Acetyltransferases/*metabolism MH - Aged MH - Animals MH - Carcinogenesis/metabolism/pathology MH - Cell Adhesion MH - Cell Line, Tumor MH - Cell Proliferation MH - *Drug Resistance, Neoplasm MH - Female MH - Glycogen Synthase Kinase 3/metabolism MH - Glycogen Synthase Kinase 3 beta MH - Humans MH - Immunohistochemistry MH - Laryngeal Neoplasms/*drug therapy/*metabolism/pathology MH - Male MH - Mice MH - Middle Aged MH - Neoplastic Stem Cells/metabolism/pathology MH - Prognosis MH - Proto-Oncogene Proteins c-akt/metabolism MH - Signal Transduction MH - Transcription Factors/*metabolism MH - beta Catenin/metabolism PMC - PMC4237250 EDAT- 2014/10/17 06:00 MHDA- 2015/06/19 06:00 PMCR- 2014/10/01 CRDT- 2014/10/17 06:00 PHST- 2014/03/27 00:00 [received] PHST- 2014/08/30 00:00 [revised] PHST- 2014/09/04 00:00 [accepted] PHST- 2014/10/17 06:00 [entrez] PHST- 2014/10/17 06:00 [pubmed] PHST- 2015/06/19 06:00 [medline] PHST- 2014/10/01 00:00 [pmc-release] AID - cddis2014424 [pii] AID - 10.1038/cddis.2014.424 [doi] PST - epublish SO - Cell Death Dis. 2014 Oct 16;5(10):e1468. doi: 10.1038/cddis.2014.424.