title: Overexpression of TRIP6 promotes tumor proliferation and reverses cell adhesion-mediated drug resistance (CAM-DR) via regulating nuclear p27(Kip1) expression in non-Hodgkin's lymphoma.
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 p27(Kip1) expression by decreasing phosphorylation of p27(Kip1) 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.
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Xiaobing
authors: X
authors: Miao
authors: Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Xiaohong
authors: X
authors: Xu
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Yaxun
authors: Y
authors: Wu
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Xinghua
authors: X
authors: Zhu
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Xudong
authors: X
authors: Chen
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Chunsun
authors: C
authors: Li
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Xiaoyun
authors: X
authors: Lu
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Yali
authors: Y
authors: Chen
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Yushan
authors: Y
authors: Liu
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors: Jieyu
authors: J
authors: Huang
authors: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China. wangyuchannt@126.com.
authors: Yuchan
authors: Y
authors: Wang
authors: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China. hesongnt@126.com.
authors: Song
authors: S
authors: He
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000368:Aged; D002448:Cell Adhesion; D002453:Cell Cycle; D049109:Cell Proliferation; D002470:Cell Survival; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D060588:LIM Domain Proteins / Q000378:metabolism*; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010641:Phenotype; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex; D014157:Transcription Factors / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C436291:CDKN1B protein, human; D060588:LIM Domain Proteins; C092282:PSMC5 protein, human; D014157:Transcription Factors; D050760:Cyclin-Dependent Kinase Inhibitor p27; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: Cell adhesion-mediated drug resistance (CAM-DR); Non-Hodgkin’s lymphoma (NHL); Proliferation; TRIP6; p27Kip1