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Effect of GNAQ alteration on RANKL-induced osteoclastogenesis in human non-small-cell lung cancer

AIMS: Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate...

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Autores principales: Choi, Ji-Yoon, Lee, Yun Sun, Shim, Da Mi, Seo, Sung Wook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229297/
https://www.ncbi.nlm.nih.gov/pubmed/32435453
http://dx.doi.org/10.1302/2046-3758.91.BJR-2019-0085.R2
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author Choi, Ji-Yoon
Lee, Yun Sun
Shim, Da Mi
Seo, Sung Wook
author_facet Choi, Ji-Yoon
Lee, Yun Sun
Shim, Da Mi
Seo, Sung Wook
author_sort Choi, Ji-Yoon
collection PubMed
description AIMS: Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells. METHODS: We investigated the specific role of GNAQ using GNAQ wild-type cell lines (non-small-cell lung cancer cell lines; A549 cell lines), GNAQ knockdown cell lines, and patient-derived cancer cells. We evaluated GNAQ, RANKL, macrophage colony-stimulating factor (M-CSF), nuclear transcription factor-κB (NF-κB), inhibitor of NF-κB (IκB), and protein kinase B (Akt) signalling in the GNAQ wild-type and the GNAQ-knockdown cells. Osteoclastogenesis was also evaluated in both cell lines. RESULTS: In the GNAQ-knockdown cells, RANKL expression was significantly upregulated (p < 0.001). The expression levels of M-CSF were also significantly increased in the GNAQ-knockdown cells compared with control cells (p < 0.001). GNAQ knockdown cells were highly sensitive to tumour necrosis factor alpha (TNF-α) and showed significant activation of the NF-κB pathway. The expression levels of RANKL were markedly increased in GNAQ mutant compared with GNAQ wild-type in patient-derived tumour tissues. CONCLUSION: The present study reveals that the alterations of GNAQ activate NF-κB pathway in cancers, which increase RANKL and M-CSF expression and induce osteoclastogenesis in cancers. Cite this article: Bone Joint Res. 2020;9(1):29–35.
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spelling pubmed-72292972020-05-20 Effect of GNAQ alteration on RANKL-induced osteoclastogenesis in human non-small-cell lung cancer Choi, Ji-Yoon Lee, Yun Sun Shim, Da Mi Seo, Sung Wook Bone Joint Res Bone Biology AIMS: Receptor activator of nuclear factor-κB ligand (RANKL) is a key molecule that is expressed in bone stromal cells and is associated with metastasis and poor prognosis in many cancers. However, cancer cells that directly express RANKL have yet to be unveiled. The current study sought to evaluate how a single subunit of G protein, guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), transforms cancer cells into RANKL-expressing cancer cells. METHODS: We investigated the specific role of GNAQ using GNAQ wild-type cell lines (non-small-cell lung cancer cell lines; A549 cell lines), GNAQ knockdown cell lines, and patient-derived cancer cells. We evaluated GNAQ, RANKL, macrophage colony-stimulating factor (M-CSF), nuclear transcription factor-κB (NF-κB), inhibitor of NF-κB (IκB), and protein kinase B (Akt) signalling in the GNAQ wild-type and the GNAQ-knockdown cells. Osteoclastogenesis was also evaluated in both cell lines. RESULTS: In the GNAQ-knockdown cells, RANKL expression was significantly upregulated (p < 0.001). The expression levels of M-CSF were also significantly increased in the GNAQ-knockdown cells compared with control cells (p < 0.001). GNAQ knockdown cells were highly sensitive to tumour necrosis factor alpha (TNF-α) and showed significant activation of the NF-κB pathway. The expression levels of RANKL were markedly increased in GNAQ mutant compared with GNAQ wild-type in patient-derived tumour tissues. CONCLUSION: The present study reveals that the alterations of GNAQ activate NF-κB pathway in cancers, which increase RANKL and M-CSF expression and induce osteoclastogenesis in cancers. Cite this article: Bone Joint Res. 2020;9(1):29–35. 2020-05-16 /pmc/articles/PMC7229297/ /pubmed/32435453 http://dx.doi.org/10.1302/2046-3758.91.BJR-2019-0085.R2 Text en © 2020 Author(s) et al Open Access This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credted. See https://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Bone Biology
Choi, Ji-Yoon
Lee, Yun Sun
Shim, Da Mi
Seo, Sung Wook
Effect of GNAQ alteration on RANKL-induced osteoclastogenesis in human non-small-cell lung cancer
title Effect of GNAQ alteration on RANKL-induced osteoclastogenesis in human non-small-cell lung cancer
title_full Effect of GNAQ alteration on RANKL-induced osteoclastogenesis in human non-small-cell lung cancer
title_fullStr Effect of GNAQ alteration on RANKL-induced osteoclastogenesis in human non-small-cell lung cancer
title_full_unstemmed Effect of GNAQ alteration on RANKL-induced osteoclastogenesis in human non-small-cell lung cancer
title_short Effect of GNAQ alteration on RANKL-induced osteoclastogenesis in human non-small-cell lung cancer
title_sort effect of gnaq alteration on rankl-induced osteoclastogenesis in human non-small-cell lung cancer
topic Bone Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229297/
https://www.ncbi.nlm.nih.gov/pubmed/32435453
http://dx.doi.org/10.1302/2046-3758.91.BJR-2019-0085.R2
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