TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer

Banerjee, Rajat; Russo, Nickole; Liu, Min; Basrur, Venkatesha; Bellile, Emily L.; Palanisamy, Nallasivam; Scanlon, Christina Springstead; Tubergen, Elizabeth Van; Inglehart, Ronald; Metwally, Tarek; Mani, Ram S.; Yocum, Anastasia K.; Nyati, Mukesh K.; Castilho, Rogerio M.; Varambally, Sooryanarayana; Chinnaiyan, Arul M.; D’Silva, Nisha J.

doi:10.1038/ncomms5527

Cited by 111 publications

(160 citation statements)

References 62 publications

(87 reference statements)

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“…The present report revealed that TRIP13 was highly expressed in CRC tumor tissues and various CRC cell lines. High expression of TRIP13 has also been reported in head and neck cancer, as well as in prostate cancer (20,28), indicating that TRIP13 may be overexpressed in a variety of cancers, similar to other kinetochore-localized proteins (25)(26)(27). Together with the current results, those studies suggest that TRIP13 is important in the progression of multiple cancers.…”

Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

“…Defects in the SAC pathway induce failure in chromosome separation and result in aneuploidy, which eventually leads to cellular apoptosis or transformation (19). TRIP13 was also reported to promote nonhomologous end-joining, and its overexpression resulted in cellular transformation and resistance to chemotherapeutic agents, indicating that aberrant expression of TRIP13 may be associated with tumor progression (20).The present study examined whether TRIP13 has a tumor-promoting function in colorectal cancer (CRC) using human CRC tissue samples and cell lines. The results demonstrated that TRIP13 is highly expressed in CRC tissues and that its depletion suppresses the malignant characteristics of CRC cells.…”

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confidence: 99%

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TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

et al. 2016

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Abstract. Thyroid hormone receptor interactor 13 (TRIP13) is a member of the ATPases associated with various cellular activities family of proteins and is highly conserved in a wide range of species. Recent studies have demonstrated that TRIP13 is critical for the inactivation of the spindle assembly checkpoint and is associated with the progression of certain cancers. In the present study, the role of TRIP13 in colorectal cancer (CRC) was examined. Reverse transcription-quantitative polymerase chain reaction analysis revealed that TRIP13 messenger RNA was highly expressed in multiple CRC tissues. The depletion of TRIP13 in CRC cells suppressed cell proliferation, migration and invasion. To determine whether the catalytic activity of TRIP13 was critical for cancer progression, an inactive mutant of TRIP13 was expressed in CRC cells. The invasion of cancer cells that expressed the mutant TRIP13 was significantly reduced compared with that of the wild type TRIP13-expressing cancer cells. These results indicate that TRIP13 could be a potential target for CRC treatment. IntroductionThe ATPases associated with various cellular activities (AAA+) family of proteins comprises a functionally different group of enzymes that are involved in an array of cellular processes, including protein degradation, protein-complex disassembly and DNA replication (1). The AAA+ proteins are present in all kingdoms, and are characterized by the presence of conserved AAA+ domains that contain Walker A and Walker B motifs, followed by a conserved region called second region of homology (2). The majority of AAA+ proteins form hexamers to exert their biological functions. The chemical energy generated by adenosine triphosphate (ATP) hydrolysis by this family of proteins induces conformational changes in the substrate proteins to modulate their functions (3,4).A previous study reported that certain AAA+ enzymes are associated with tumor progression (5). For example, reptin [also known as RuvB-like (RUVBL) 2] and pontin (RUVBL1) have been demonstrated to be overexpressed in several tumors (5). These proteins interact with c-Myc or β-catenin, thus modulating their transcriptional activities to promote tumor progression (6). AAA+ proteins hydrolyze ATP, and thus, chemical inhibitors that disrupt the activities of cancer-associated AAA+ proteins may represent promising anti-cancer drugs.Thyroid hormone receptor interactor 13 (TRIP13, also known as 16E1BP and pachytene checkpoint 2) is a member of the AAA+ family proteins and is conserved in a wide range of species (7). It was first identified as a protein that interacts with human papilloma virus E1 proteins by a yeast two-hybrid analysis, but the physiological function of the interaction remains unknown (7). Accumulating studies have demonstrated that TRIP13 plays pivotal roles in meiotic recombination and DNA repair in plants, yeast, worms and mice (8-12). TRIP13 forms a stable hexameric ring, and ATP binding, as well as ATP hydrolysis, are critical for the function of the protein (13). Previous...

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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confidence: 99%

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TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

et al. 2016

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“…Instead, most of the work involving AGS7/Trip13, which is also a homolog to mouse pachytene checkpoint 2 (mPCH2), has focused on its AAAATPase activity with emphasis on the mechanistic control of DNA damage repair (Bolcun-Filas et al, 2014), cell-cycle checkpoint, kinetochore control (Tipton et al, 2012;Wang et al, 2014), and meiotic recombination (Li and Schimenti, 2007;Roig et al, 2010). These initial studies led to recent highimpact findings regarding AGS7/Trip13 in reproductive cell biology (Li and Schimenti, 2007;Roig et al, 2010) and cancer (Banerjee et al, 2014).…”

Section: Group III Ags Proteinsmentioning

confidence: 99%

Activators of G Protein Signaling in the Kidney

Park

2015

J Pharmacol Exp Ther

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Heterotrimeric G proteins play a crucial role in regulating signal processing to maintain normal cellular homeostasis, and subtle perturbations in its activity can potentially lead to the pathogenesis of renal disorders or diseases. Cell-surface receptors and accessory proteins, which normally modify and organize the coupling of individual G protein subunits, contribute to the regulation of heterotrimeric G protein activity and their convergence and/or divergence of downstream signaling initiated by effector systems. Activators of G protein signaling (AGS) are a family of accessory proteins that intervene at multiple distinct points during the activation-inactivation cycle of G proteins, even in the absence of receptor stimulation. Perturbations in the expression of individual AGS proteins have been reported to modulate signal transduction pathways in a wide array of diseases and disorders within the brain, heart, immune system, and more recently, the kidney. This review will provide an overview of the expression profile, localization, and putative biologic role of the AGS family in the context of normal and diseased states of the kidney.

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“…The DNA-PKcs uses ligase IV to mediate ligation; this leads to end processing that seals the duplex DNA binding site (9). Recent studies report that activating NHEJ repair through the interaction of the DNA-PKcs with its partners induces chemoresistance in cancer cells (10) and that inhibiting it induces chemosensitization (11). Thus, targeting the NHEJ pathway is an innovative cancer therapy strategy (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

RON Nuclear Translocation under Hypoxia Potentiates Chemoresistance to DNA Double-Strand Break–Inducing Anticancer Drugs

Chang

Huang

et al. 2016

Molecular Cancer Therapeutics

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Tumor hypoxia is associated with radioresistance, chemoresistance, and metastasis, which eventually lead to cancer progression and a poor patient prognosis. RON [also known as macrophagestimulating protein receptor (MST1R)] belongs to the c-MET [also known as hepatocyte growth factor receptor (HGFR)] receptor tyrosine kinase (RTK) superfamily. To identify the interaction partners of RON nuclear translocation in response to hypoxia, the nuclear extract of TSGH8301 bladder cancer cells was immunoprecipitated for tandem mass profiling analysis. Nuclear RON interacted with adenosine triphosphate (ATP)-dependent DNA helicase 2 (Ku70) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to activate nonhomologous end joining (NHEJ) DNA repair. The interaction was time dependent, extending 3 to 24 hours posthypoxia or until the components had been exposed to the chemotherapeutic drugs doxorubicin and epirubicin. Stable knockdown experiments in vitro suggest the importance of RON for the chemoresistance of cancer cells under hypoxia. In addition, the tyrosine kinase domain of nuclear RON is crucial for interaction with Ku70 under hypoxia. J82 cells transfected with RON showed a survival advantage in the presence of epirubicin and hypoxia. This suggests that nuclear RON activates NHEJ repair by interacting with Ku70/DNA-PKcs and inhibiting RON activity to increase cancer cell chemosensitivity.Mol Cancer Ther; 15(2); 276-86. Ó2016 AACR.

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TRIP13 promotes error-prone nonhomologous end joining and induces chemoresistance in head and neck cancer

Cited by 111 publications

References 62 publications

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

TRIP13 is expressed in colorectal cancer and promotes cancer cell invasion

Activators of G Protein Signaling in the Kidney

RON Nuclear Translocation under Hypoxia Potentiates Chemoresistance to DNA Double-Strand Break–Inducing Anticancer Drugs

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