open access

Vol 68, No 6 (2017)
Original Paper
Published online: 2017-09-18
Submitted: 2017-02-03
Accepted: 2017-03-07
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The significance of TRIP11 and T3 signalling pathway in renal cancer progression and survival of patients

Piotr Popławski, Agnieszka Piekiełko-Witkowska, Alicja Nauman
DOI: 10.5603/EP.a2017.0052
·
Pubmed: 29022645
·
Endokrynologia Polska 2017;68(6):631-641.

open access

Vol 68, No 6 (2017)
Original Paper
Published online: 2017-09-18
Submitted: 2017-02-03
Accepted: 2017-03-07

Abstract

Introduction: TRIP11 is a multifunctional protein localizing either to Golgi apparatus, acting as a golgin, or in the nucleus, acting as coactivator of transcription mediated by thyroid hormone receptor (THR) and hypoxia induced factor (HIF). Triiodothyronine (T3) regulates nuclear localization of TRIP11 by inducing its phosphorylation. The exact mechanism of this regulation unknown. The expressions of THR and HIF are disturbed in various cancers, including renal cell cancer (RCC). In this study we aimed to analyze: 1) the mechanism of T3-dependent subcellular localization of TRIP11; 2) the significance of TRIP11 and T3 signaling pathway in RCC progression. Material and methods: TRIP11 subcellular localization was analyzed using immunocytochemistry in RCC-derived cell line treated with T3, T3-agarose and PI3K inhibitor, wortmannin. The expressions of TRIP11 and genes involved in T3 signaling and hypoxia were investigated using qPRC in 36 pairs of RCC tumor-control samples, followed by validation/survival analysis in an independent cohort of >450 renal cancer patients. Results: Wortmannin disrupted T3-dependent nuclear transport of TRIP11. T3-agarose did not change TRIP11 localization, precluding extracellular T3-mediated mechanism. The expressions of TRIP11, HIF-1β, THRA, THRB, FURIN, VEGFA, and GLUT1 were disturbed in renal cancer. Expressions of TRIP11 and HIF-1β correlated with tumor grades. Decreased expressions of TRIP11, THRA, and THRB correlated with poor survival of RCC patients. Conclusions: 1) T3 induces nuclear TRIP11 localization via PI3K-dependent mechanism; 2) disturbed expression of T3 signaling pathway genes correlates with RCC progression. The specific mechanisms by which altered T3 signaling may contribute to RCC progression require further investigation.

Abstract

Introduction: TRIP11 is a multifunctional protein localizing either to Golgi apparatus, acting as a golgin, or in the nucleus, acting as coactivator of transcription mediated by thyroid hormone receptor (THR) and hypoxia induced factor (HIF). Triiodothyronine (T3) regulates nuclear localization of TRIP11 by inducing its phosphorylation. The exact mechanism of this regulation unknown. The expressions of THR and HIF are disturbed in various cancers, including renal cell cancer (RCC). In this study we aimed to analyze: 1) the mechanism of T3-dependent subcellular localization of TRIP11; 2) the significance of TRIP11 and T3 signaling pathway in RCC progression. Material and methods: TRIP11 subcellular localization was analyzed using immunocytochemistry in RCC-derived cell line treated with T3, T3-agarose and PI3K inhibitor, wortmannin. The expressions of TRIP11 and genes involved in T3 signaling and hypoxia were investigated using qPRC in 36 pairs of RCC tumor-control samples, followed by validation/survival analysis in an independent cohort of >450 renal cancer patients. Results: Wortmannin disrupted T3-dependent nuclear transport of TRIP11. T3-agarose did not change TRIP11 localization, precluding extracellular T3-mediated mechanism. The expressions of TRIP11, HIF-1β, THRA, THRB, FURIN, VEGFA, and GLUT1 were disturbed in renal cancer. Expressions of TRIP11 and HIF-1β correlated with tumor grades. Decreased expressions of TRIP11, THRA, and THRB correlated with poor survival of RCC patients. Conclusions: 1) T3 induces nuclear TRIP11 localization via PI3K-dependent mechanism; 2) disturbed expression of T3 signaling pathway genes correlates with RCC progression. The specific mechanisms by which altered T3 signaling may contribute to RCC progression require further investigation.
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Keywords

RCC, thyroid hormones, hypoxia, TRIP11

About this article
Title

The significance of TRIP11 and T3 signalling pathway in renal cancer progression and survival of patients

Journal

Endokrynologia Polska

Issue

Vol 68, No 6 (2017)

Pages

631-641

Published online

2017-09-18

DOI

10.5603/EP.a2017.0052

Pubmed

29022645

Bibliographic record

Endokrynologia Polska 2017;68(6):631-641.

Keywords

RCC
thyroid hormones
hypoxia
TRIP11

Authors

Piotr Popławski
Agnieszka Piekiełko-Witkowska
Alicja Nauman

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