Tumor Suppressor REIC/DKK-3 and Co-chaperone SGTA: Their Interaction and Roles in the Androgen Sensitivity

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Dec 15

PMID 26658102

Citations 5

Authors

Kazuhiko Ochiai

Masami Morimatsu

Yuiko Kato

Toshina Ishiguro-Oonuma

Chihiro Udagawa

Oumaporn Rungsuriyawiboon

Daigo Azakami

Masaki Michishita

Yuichi Ariyoshi

Hideo Ueki

Yasutomo Nasu

Hiromi Kumon

Masami Watanabe

Toshinori Omi

Affiliations

Soon will be listed here.

Abstract

REIC/DKK-3 is a tumor suppressor, however, its intracellular physiological functions and interacting molecules have not been fully clarified. Using yeast two-hybrid screening, we found that small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA), known as a negative modulator of cytoplasmic androgen receptor (AR) signaling, is a novel interacting partner of REIC/DKK-3. Mammalian two-hybrid and pull-down assay results indicated that the SGTA-REIC/DKK-3 interaction involved the N-terminal regions of both REIC/DKK-3 and SGTA and that REIC/DKK-3 interfered with the dimerization of SGTA, which is a component of the AR complex and a suppressor of dynein motor-dependent AR transport and signaling. A reporter assay in human prostate cancer cells that displayed suppressed AR signaling by SGTA showed recovery of AR signaling by REIC/DKK-3 expression. Considering these results and our previous data that REIC/DKK-3 interacts with the dynein light chain TCTEX-1, we propose that the REIC/DKK-3 protein interferes with SGTA dimerization, promotes dynein-dependent AR transport and then upregulates AR signaling.

Citing Articles

Tumor suppressor REIC/Dkk-3 and its interacting protein SGTA inhibit glucocorticoid receptor to nuclear transport.

Iwata T, Sadahira T, Ochiai K, Ueki H, Sasaki T, Haung P Exp Ther Med. 2020; 20(2):1739-1745.

PMID: 32765682 PMC: 7388570. DOI: 10.3892/etm.2020.8819.

MiR-425 Promotes Migration and Invasion in Bladder Cancer by Targeting Dickkopf 3.

Ning J, Yu W, Cheng F, Rao T, Ruan Y J Cancer. 2020; 11(12):3424-3432.

PMID: 32284738 PMC: 7150467. DOI: 10.7150/jca.40233.

DYNC1I1 Promotes the Proliferation and Migration of Gastric Cancer by Up-Regulating IL-6 Expression.

Gong L, Wen T, Li Z, Xin X, Che X, Wang J Front Oncol. 2019; 9:491.

PMID: 31249807 PMC: 6582752. DOI: 10.3389/fonc.2019.00491.

Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines.

Kato Y, Ochiai K, Kawakami S, Nakao N, Azakami D, Bonkobara M BMC Vet Res. 2017; 13(1):170.

PMID: 28599655 PMC: 5466802. DOI: 10.1186/s12917-017-1094-4.

How Polyomaviruses Exploit the ERAD Machinery to Cause Infection.

Dupzyk A, Tsai B Viruses. 2016; 8(9).

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