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Contribution of TIP30 to chemoresistance in laryngeal carcinoma.

Zhu M, Yin F, Yang L, Chen S, Chen R, Zhou X, Jing W, Fan X, Jia R, Wang H, Zheng H, Zhao J, Guo Y - Cell Death Dis (2014)

Bottom Line: We showed that TIP30 expression decreased significantly in drug-selected cells (DSCs) of laryngeal carcinoma.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.

View Article: PubMed Central - PubMed

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.

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.

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Low TIP30 expression predicts a poor prognosis in patients with laryngeal carcinoma. Kaplan–Meier survival curves showing overall (left) and recurrence-free survival rates (right) of 105 patients with laryngeal carcinoma between the TIP30-high versus TIP30-low-expressing groups (log-rank test)
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fig6: Low TIP30 expression predicts a poor prognosis in patients with laryngeal carcinoma. Kaplan–Meier survival curves showing overall (left) and recurrence-free survival rates (right) of 105 patients with laryngeal carcinoma between the TIP30-high versus TIP30-low-expressing groups (log-rank test)

Mentions: The potential associations between TIP30 immunostaining and overall survival (OS) and recurrence-free survival (RFS) were retrospectively evaluated in these patients. A Kaplan–Meier analysis showed that OS (P=0.022) and RFS (P=0.002) were significantly better among patients with high TIP30 staining compared with those with low TIP30 staining (Figure 6). A univariate analysis showed that sex, age, T stage and clinical stage had no prognostic significance for RFS and OS. However, tumour site, histologic differentiation and TIP30 expression were predictors of RFS and OS, whereas lymph node metastasis only had prognostic significance for RFS (Supplementary Table S2). In a multivariate analysis, we found that lymph node metastasis, histologic differentiation and TIP30 expression were independent prognostic factors for RFS. Histologic differentiation and TIP30 expression also had independent prognostic value for OS (Supplementary Table S3).


Contribution of TIP30 to chemoresistance in laryngeal carcinoma.

Zhu M, Yin F, Yang L, Chen S, Chen R, Zhou X, Jing W, Fan X, Jia R, Wang H, Zheng H, Zhao J, Guo Y - Cell Death Dis (2014)

Low TIP30 expression predicts a poor prognosis in patients with laryngeal carcinoma. Kaplan–Meier survival curves showing overall (left) and recurrence-free survival rates (right) of 105 patients with laryngeal carcinoma between the TIP30-high versus TIP30-low-expressing groups (log-rank test)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4237250&req=5

fig6: Low TIP30 expression predicts a poor prognosis in patients with laryngeal carcinoma. Kaplan–Meier survival curves showing overall (left) and recurrence-free survival rates (right) of 105 patients with laryngeal carcinoma between the TIP30-high versus TIP30-low-expressing groups (log-rank test)
Mentions: The potential associations between TIP30 immunostaining and overall survival (OS) and recurrence-free survival (RFS) were retrospectively evaluated in these patients. A Kaplan–Meier analysis showed that OS (P=0.022) and RFS (P=0.002) were significantly better among patients with high TIP30 staining compared with those with low TIP30 staining (Figure 6). A univariate analysis showed that sex, age, T stage and clinical stage had no prognostic significance for RFS and OS. However, tumour site, histologic differentiation and TIP30 expression were predictors of RFS and OS, whereas lymph node metastasis only had prognostic significance for RFS (Supplementary Table S2). In a multivariate analysis, we found that lymph node metastasis, histologic differentiation and TIP30 expression were independent prognostic factors for RFS. Histologic differentiation and TIP30 expression also had independent prognostic value for OS (Supplementary Table S3).

Bottom Line: We showed that TIP30 expression decreased significantly in drug-selected cells (DSCs) of laryngeal carcinoma.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.

View Article: PubMed Central - PubMed

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.

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.

Show MeSH
Related in: MedlinePlus