Membrane‐tethered Notch1 exhibits oncogenic property via activation of EGFR–PI3K–AKT pathway in oral squamous cell carcinoma

AbstractObjective: This research aimed to explore the function of protease activated receptor 2 (PAR-2) in oral squamous cell carcinoma (OSCC) development and progression, as well as underlying molecular mechanism.Methods: Tissue samples were collected from 115 OSCC patients. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of PAR-2 mRNA in OSCC tissues and cells. MTT and Transwell assays were used to detect the proliferation, migration, and invasion of OSCC cells, respectively. Western blot was performed to determine protein expression.Results: The expression of PAR-2 mRNA was up-regulated in OSCC tissue and cells (P<0.01), and its mRNA level was obviously correlated to tumor differentiation and TNM stage in OSCC (P<0.05 for both). The activation of PAR-2 with PAR-2AP (PAR-2 agonist) significantly promoted the proliferation, migration, and invasion of OSCC cells, while its knockout could inhibit malignant behaviors of OSCC cells (P<0.05). Excessive activation of PAR-2 enhanced phosphorylation level of PI3K, AKT, and mTOR revealing the activation of PI3K/AKT pathway. Moreover, LY294002, the inhibitor of PI3K/AKT pathway, could reverse oncogenic action caused by PAR-2 activation.Conclusion: PAR-2 can promote OSCC growth and progression via activating PI3K/AKT signaling pathway.

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Mutational analysis of PTEN/PIK3CA/AKT pathway in oral squamous cell carcinoma

Oral Oncology ◽

10.1016/j.oraloncology.2011.07.013 ◽

2011 ◽

Vol 47 (10) ◽

pp. 946-950 ◽

Cited By ~ 37

Author(s):

Yoram Cohen ◽

Nitza Goldenberg-Cohen ◽

Bruria Shalmon ◽

Tali Shani ◽

Shirley Oren ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Mutational Analysis ◽

Akt Pathway

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LncRNA FENDRR in Carcinoma-Associated Fibroblasts Regulates the Angiogenesis of Oral Squamous Cell Carcinoma Through the PI3K/AKT Pathway

Frontiers in Oncology ◽

10.3389/fonc.2021.616576 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yuming Xu ◽

Erhui Jiang ◽

Zhe Shao ◽

Zhengjun Shang

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Umbilical Vein ◽

Quantitative Polymerase Chain Reaction ◽

Inhibitory Effect ◽

Akt Pathway ◽

Normal Tissues ◽

Carcinoma Associated Fibroblasts

Angiogenesis is essential for the development of tumors. Studies have shown that carcinoma-associated fibroblasts (CAFs) are involved in regulating tumor angiogenesis, but the mechanism remains unclear. Recently, long noncoding RNAs (lncRNAs) have been proved to play an important role in the angiogenesis of various tumors. However, there is currently no research involving the regulation of CAFs on the angiogenesis of oral squamous cell carcinoma (OSCC) mediated by lncRNAs. By analyzing microarray data, we identified that the expression of lncRNA FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) in OSCC patients is downregulated, compared to that in normal tissues. Quantitative polymerase chain reaction (qPCR) results demonstrated that FENDRR expression is lower in CAFs compared to normal fibroblasts (NFs) of OSCC patients. KEGG pathway analysis revealed that some genes differentially expressed between CAFs and NFs of HNSCC patients are enriched to the PI3K/AKT pathway. Further experiments confirmed that the downregulation of FENDRR can activate the PI3K/AKT pathway in NFs and enhances the expression of matrix metalloproteinase 9 (MMP9). The overexpression of FENDRR had the opposite effect. Besides, we co-cultured human umbilical vein endothelial cells (HUVECs) with CAFs, and the tube-forming ability of HUVECs co-cultured with CAFs overexpressing FENDRR decreased significantly. However, activation of the AKT pathway of CAFs overexpressing FENDRR can weaken the inhibitory effect of FENDRR on angiogenesis. In summary, our experiments are focused on the influence of lncRNAs in CAFs on OSCC angiogenesis for the first time and prove that FENDRR mediates CAFs’ regulation of OSCC angiogenesis through the PI3K/AKT pathway.

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