Gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines.
Oral squamous cell carcinoma (OSCC) ranks among the top ten most prevalent cancers worldwide. Like most head and neck squamous cell carcinomas (HNSCCs), OSCC is highly inflammatory and aggressive. However, the signaling pathways triggering the activation of its inflammatory processes remain elusive....
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/4b2fc34c47274e9c8372161463be10f3 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:4b2fc34c47274e9c8372161463be10f3 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:4b2fc34c47274e9c8372161463be10f32021-11-18T07:42:33ZGα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines.1932-620310.1371/journal.pone.0066133https://doaj.org/article/4b2fc34c47274e9c8372161463be10f32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762476/?tool=EBIhttps://doaj.org/toc/1932-6203Oral squamous cell carcinoma (OSCC) ranks among the top ten most prevalent cancers worldwide. Like most head and neck squamous cell carcinomas (HNSCCs), OSCC is highly inflammatory and aggressive. However, the signaling pathways triggering the activation of its inflammatory processes remain elusive. G protein-coupled receptor signaling regulates the inflammatory response and invasiveness of cancers, but it remains unclear whether Gα12 is a critical player in the inflammatory cytokine pathway during the tumorigenesis of OSCC. This study was undertaken to determine the role of Gα12 signaling in the regulation of proinflammatory cytokines in their mediation of OSCC invasion. We found that both the transcription and protein levels of Gα12 are up-regulated in OSCC tumors. The elevated Gα12 expressions in OSCC patients also correlated with extra-capsular spread, an indicator of tumor invasiveness in HNSCCs. This clinical finding was supported by the studies of overexpression and RNAi knockdown of Gα12 in OSCC cells, which demonstrated that Gα12 promoted tumor cell migration and invasion. To understand how Gα12 modulates OSCC invasiveness, we analyzed key biological processes in microarray data upon depletion of Gα12 and found that cytokine- and other immune-related pathways were severely impaired. Importantly, the mRNA levels of IL-6 and IL-8 proinflammatory cytokines in clinical samples were found to be significantly correlated with the increased Gα12 levels, suggesting a potential role of Gα12 in modulating the IL-6 and IL-8 expressions. Supporting this hypothesis, overexpression or RNAi knockdown of Gα12 in OSCC cell lines both showed that Gα12 positively regulated the mRNA and protein levels of IL-6 and IL-8. Finally, we demonstrated that the Gα12 promotion of tumor cell invasiveness was suppressed by the neutralization of IL-6 and IL-8 in OSCC cells. Together, these findings suggest that Gα12 drives OSCC invasion through the up-regulation of IL-6 and IL-8 cytokines.Shiou-Ling JianHsin-Yi HsiehChun-Ta LiaoTzu-Chen YenShu-Wei NienAnn-Joy ChengJyh-Lyh JuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e66133 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Shiou-Ling Jian Hsin-Yi Hsieh Chun-Ta Liao Tzu-Chen Yen Shu-Wei Nien Ann-Joy Cheng Jyh-Lyh Juang Gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. |
| description |
Oral squamous cell carcinoma (OSCC) ranks among the top ten most prevalent cancers worldwide. Like most head and neck squamous cell carcinomas (HNSCCs), OSCC is highly inflammatory and aggressive. However, the signaling pathways triggering the activation of its inflammatory processes remain elusive. G protein-coupled receptor signaling regulates the inflammatory response and invasiveness of cancers, but it remains unclear whether Gα12 is a critical player in the inflammatory cytokine pathway during the tumorigenesis of OSCC. This study was undertaken to determine the role of Gα12 signaling in the regulation of proinflammatory cytokines in their mediation of OSCC invasion. We found that both the transcription and protein levels of Gα12 are up-regulated in OSCC tumors. The elevated Gα12 expressions in OSCC patients also correlated with extra-capsular spread, an indicator of tumor invasiveness in HNSCCs. This clinical finding was supported by the studies of overexpression and RNAi knockdown of Gα12 in OSCC cells, which demonstrated that Gα12 promoted tumor cell migration and invasion. To understand how Gα12 modulates OSCC invasiveness, we analyzed key biological processes in microarray data upon depletion of Gα12 and found that cytokine- and other immune-related pathways were severely impaired. Importantly, the mRNA levels of IL-6 and IL-8 proinflammatory cytokines in clinical samples were found to be significantly correlated with the increased Gα12 levels, suggesting a potential role of Gα12 in modulating the IL-6 and IL-8 expressions. Supporting this hypothesis, overexpression or RNAi knockdown of Gα12 in OSCC cell lines both showed that Gα12 positively regulated the mRNA and protein levels of IL-6 and IL-8. Finally, we demonstrated that the Gα12 promotion of tumor cell invasiveness was suppressed by the neutralization of IL-6 and IL-8 in OSCC cells. Together, these findings suggest that Gα12 drives OSCC invasion through the up-regulation of IL-6 and IL-8 cytokines. |
| format |
article |
| author |
Shiou-Ling Jian Hsin-Yi Hsieh Chun-Ta Liao Tzu-Chen Yen Shu-Wei Nien Ann-Joy Cheng Jyh-Lyh Juang |
| author_facet |
Shiou-Ling Jian Hsin-Yi Hsieh Chun-Ta Liao Tzu-Chen Yen Shu-Wei Nien Ann-Joy Cheng Jyh-Lyh Juang |
| author_sort |
Shiou-Ling Jian |
| title |
Gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. |
| title_short |
Gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. |
| title_full |
Gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. |
| title_fullStr |
Gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. |
| title_full_unstemmed |
Gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. |
| title_sort |
gα₁₂ drives invasion of oral squamous cell carcinoma through up-regulation of proinflammatory cytokines. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/4b2fc34c47274e9c8372161463be10f3 |
| work_keys_str_mv |
AT shioulingjian ga12drivesinvasionoforalsquamouscellcarcinomathroughupregulationofproinflammatorycytokines AT hsinyihsieh ga12drivesinvasionoforalsquamouscellcarcinomathroughupregulationofproinflammatorycytokines AT chuntaliao ga12drivesinvasionoforalsquamouscellcarcinomathroughupregulationofproinflammatorycytokines AT tzuchenyen ga12drivesinvasionoforalsquamouscellcarcinomathroughupregulationofproinflammatorycytokines AT shuweinien ga12drivesinvasionoforalsquamouscellcarcinomathroughupregulationofproinflammatorycytokines AT annjoycheng ga12drivesinvasionoforalsquamouscellcarcinomathroughupregulationofproinflammatorycytokines AT jyhlyhjuang ga12drivesinvasionoforalsquamouscellcarcinomathroughupregulationofproinflammatorycytokines |
| _version_ |
1718423094915235840 |