PMID- 32435453
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220414
IS  - 2046-3758 (Print)
IS  - 2046-3758 (Electronic)
IS  - 2046-3758 (Linking)
VI  - 9
IP  - 1
DP  - 2020 Jan
TI  - Effect of GNAQ alteration on RANKL-induced osteoclastogenesis in human 
      non-small-cell lung cancer.
PG  - 29-35
LID - 10.1302/2046-3758.91.BJR-2019-0085.R2 [doi]
AB  - AIMS: Receptor activator of nuclear factor-kappaB 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-kappaB (NF-kappaB), 
      inhibitor of NF-kappaB (IkappaB), 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-alpha) and showed significant activation of the NF-kappaB 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-kappaB 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.
CI  - (c) 2020 Author(s) et al.
FAU - Choi, Ji-Yoon
AU  - Choi JY
AD  - Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan 
      University, Seoul, South Korea.
FAU - Lee, Yun Sun
AU  - Lee YS
AD  - Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan 
      University, Seoul, South Korea.
FAU - Shim, Da Mi
AU  - Shim DM
AD  - Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan 
      University, Seoul, South Korea.
FAU - Seo, Sung Wook
AU  - Seo SW
AD  - Department of Orthopaedic Surgery, Samsung Medical Center, Sungkyunkwan 
      University, Seoul, South Korea.
LA  - eng
PT  - Journal Article
DEP - 20200516
PL  - England
TA  - Bone Joint Res
JT  - Bone & joint research
JID - 101586057
PMC - PMC7229297
OTO - NOTNLM
OT  - Bone
OT  - GNAQ
OT  - Lung cancer
OT  - Osteoclastogenesis
OT  - RANKL
EDAT- 2020/05/22 06:00
MHDA- 2020/05/22 06:01
PMCR- 2020/05/16
CRDT- 2020/05/22 06:00
PHST- 2020/05/22 06:00 [entrez]
PHST- 2020/05/22 06:00 [pubmed]
PHST- 2020/05/22 06:01 [medline]
PHST- 2020/05/16 00:00 [pmc-release]
AID - 10.1302_2046-3758.91.BJR-2019-0085.R2 [pii]
AID - 10.1302/2046-3758.91.BJR-2019-0085.R2 [doi]
PST - epublish
SO  - Bone Joint Res. 2020 May 16;9(1):29-35. doi: 
      10.1302/2046-3758.91.BJR-2019-0085.R2. eCollection 2020 Jan.