Homeobox B7 accelerates the cancer progression of gastric carcinoma cells by promoting epithelial-mesenchymal transition (EMT) and activating Src-FAK pathway.
SIGNIFICANCE: These findings suggest that RORC-mediated regulation of a PD-L1/ITGB6/FAK/STAT3 signaling axis in bladder cancer provides several potential therapeutic targets to prevent tumor progression.
Focal adhesion kinase 1 (FAK1) is known to promote tumor progression and metastasis by controlling cell movement, invasion, survival and the epithelial-to-mesenchymal transition in the tumor microenvironment.
Recently, Jiang and colleagues identified a key role for FAK in regulating the composition of the fibrotic and immuno-suppressive pancreatic tumour niche, and showed that FAK inhibitors can be used in combination with immune checkpoint blockade and gemcitabine chemotherapy to significantly delay pancreatic tumour progression.
Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib.
Thus, we describe novel functions for Src/FAK in mediating the EMT program and aggressiveness regulated by TGFβ, establishing the inhibition of these proteins as a possible effective approach in preventing tumour progression of <sup>V600E</sup> BRAF-expressing thyroid tumours.
In addition, Michigan Molecular Interactions searches indicated that together these proteins affect signaling pathways that regulate cell cycle and proliferation, focal adhesions, and other cellular properties that overall enhance tumor progression (including signaling pathways such as TGF-β, WNT, MAPK, and FAK).
Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression.