Abstract
Recent studies have identified that thyroid hormone receptor-interacting protein 6 (TRIP6) is implicated in tumorigenesis. However, the functional role of TRIP6 in non-Hodgkin’s lymphoma (NHL) has never been elucidated. In this study, we demonstrated that TRIP6 is reversely correlated with the clinical outcomes of NHL patients. Western blot and immunohistochemical analysis revealed that TRIP6 expression is lower in indolent lymphoma than in progressive lymphoma. Kaplan-Meier survival curves indicated that the upregulation of TRIP6 is significantly associated with poor overall survival. Moreover, patients with higher expression of TRIP6 are prone to shorter time to recurrence. Furthermore, we also found that TRIP6 can promote the proliferation of NHL cells via regulating cell cycle progression. In addition, adhesion of lymphoma cells to fibronectin (FN) decreased TRIP6 expression, which led to the upregulation of nuclear p27Kip1 expression by decreasing phosphorylation of p27Kip1 at T157. Importantly, overexpression of TRIP6 can reverse cell adhesion-mediated drug resistance (CAM-DR) phenotype in NHL. In summary, these results suggest that TRIP6 is a novel prognostic indicator for NHL patients and may shed new insights into the important role of TRIP6 in cancer development.
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Acknowledgments
This work was supported by grants from the National Natural Science Foundation of China (no. 81201858, no. 81372537) and Natural Scientific Foundation of Jiangsu Province Grant (no. BK2012231).
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Xiaobing Miao and Xiaohong Xu contributed equally to this work.
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Miao, X., Xu, X., Wu, Y. et al. Overexpression of TRIP6 promotes tumor proliferation and reverses cell adhesion-mediated drug resistance (CAM-DR) via regulating nuclear p27Kip1 expression in non-Hodgkin’s lymphoma. Tumor Biol. 37, 1369–1378 (2016). https://doi.org/10.1007/s13277-015-3939-4
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DOI: https://doi.org/10.1007/s13277-015-3939-4