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Cell death & disease

Contribution of TIP30 to chemoresistance in laryngeal carcinoma.


PMID 25321475

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.