Our data suggest that the PI3K/AKT pathway is related to cell survival and proliferation in oral squamous cell carcinoma through its interaction with Bcl-2 family members.<br />.
Alterations characteristic of adenocarcinoma (EGFR, KRAS, ALK receptor tyrosine kinase [ALK], ROS1, and serine/threonine kinase 11 [STK11]) were detected in the LCC-AD subgroup but not in LCC-SqCC, whereas squamous-lineage alterations (phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit alpha [PIK3CA], SRY-box 2 [SOX2], fibroblast growth factor receptor 1 [FGFR1], and AKT1) were detected in the LCC-SqCC subgroup but not in the LCC-AD group.
Moreover, since the PI3K/AKT/mTOR pathway is considered to be a promising target for anticancer therapy, we discuss clinical implications for the treatment of HPV-positive cervical and head and neck squamous cell carcinomas.
Increased expression of lncRNA CASC9 promotes tumor progression by suppressing autophagy-mediated cell apoptosis via the AKT/mTOR pathway in oral squamous cell carcinoma.
We divided our OSCC patients into non-metastasizing (PNM) and metastasizing (PM) groups, and the expression of total AKT, pAKT1<sup>Thr308</sup>, pAKT<sup>Ser473</sup>, GSK3β, pGSK3β<sup>Ser9</sup>, and pmTOR<sup>Ser2448</sup> was analyzed by immunohistochemistry.
In conclusion, our date indicate 1) epigenetic regulation is associated with <i>CSTA</i> gene silencing; 2) CSTA exerts tumor suppressive function through inhibiting MAPK and AKT pathways; 3) Overexpression of CSTA leads to MET and prevents TGF-β1-induced EMT by modulating the MAPK pathway; 4) CSTA may be a potential biomarker for lung SCC and tumor differentiation.
Tissue microarrays (TMAs) were used to evaluate pAKT(Ser473)/(Thr308), total protein kinase B (AKT)(pan) and phosphatase and tensin homolog (PTEN) expression in primary tumors and corresponding nodal disease in oropharyngeal SCC.
In sum, our data provide compelling evidence that miR-194 functions as a potential tumor suppressor by inhibiting the PI3K/AKT/FoxO3a signaling pathway and might sever as a potential therapeutic target for OSCC patients.
Specifically, we found that KRAS/LKB1-mutant lung adenocarcinomas responded strongly to phenformin + MLN0128 treatment, but the response of SCCs to single or combined treatment with MLN0128 was more attenuated due to acquired resistance to mTOR inhibition through modulation of the AKT-GSK signaling axis.
Moreover, blocking the whole PI3K-AKT-mTOR pathway with the PI3K/mTOR dual inhibitor BEZ235 also showed efficacy in treating this subtype of lung SqCC.
Analysis of 675 tumors revealed activation of PIK3CA and other PI3K/AKT pathway genes in 31% of squamous carcinomas and 24% of adeno- and adenosquamous tumors, predominantly at two sites (E542K, E545K) in the helical domain of the PIK3CA gene.
Expression of total Akt, Akt2 and Akt3 were frequently observed in small cell carcinoma, but phosphorylated Akt and Akt1 were more frequently observed in squamous cell carcinoma.
We therefore analyzed 102 large-cell carcinomas by immunohistochemistry for TTF-1 and ΔNp63/p40 as classifiers for adenocarcinoma and squamous cell carcinoma, respectively, and correlated the resulting subtypes with nine therapeutically relevant genetic alterations characteristic of adenocarcinoma (EGFR, KRAS, BRAF, MAP2K1/MEK1, NRAS, ERBB2/HER2 mutations and ALK rearrangements) or more common in squamous cell carcinoma (PIK3CA and AKT1 mutations).
The screen of 95 biomarker-verified SQCCs revealed no EGFR/KRAS [0%; 95% confidence interval (CI), 0%-3.8%], four PIK3CA (4%; 95% CI, 1%-10%), and one AKT1 (1%; 95% CI, 0%-5.7%) mutations.
Whereas in AC the expression and amplification of EGFR were linked to AKT activation (P< or =0.050), in SCC its expression was correlated with pSTAT3 (P=0.024).