Keratinocyte growth factor (KGF), also termed as fibroblast growth factor-7, promotes proliferation, migration, and adhesion of skin keratinocytes via binding to keratinocyte growth factor receptor (KGFR) and subsequent activation of downstream signaling including the PI3K-AKT-mTORC1 pathway. Here, we found that the α-subunits of the G proteins (Gαi1/3) and growth factor receptor binding 2-associated binding protein 1 (Gab1) are required for this activation process. With KGF stimulation, Gαi1/3 formed a complex with KGFR and was required for subsequent Gab1 recruitment, phosphorylation, and following PI3K-p85 activation. In addition, Gαi1/3 short hairpin RNA knockdown largely inhibited KGF-induced cell proliferation, migration, and the accumulation of cyclin D1/fibronectin in cultured skin keratinocytes. Furthermore, we observed increased expression of Gαi1/3 in wounded human skin and keloid skin tissues, suggesting the possible involvement of Gαi1/3 in wound healing and keloid formation. Overall, we suggest that Gαi1/3 proteins lie downstream of KGFR, but upstream of Gab1-mediated activation of PI3K-AKT-mTORC1 signaling, thus revealing a role for Gαi proteins in mediating KGFR signaling, cell migration, and possible wound healing.

GSDMD may protect against cell proliferation of GC, and it may be used as a diagnostic and treatment strategy for GC.

Sorafenib in combination with TACE should be considered a safe and effective therapy for advanced HCC. Further validation of the new subgroup of BCLC-C stage is warranted in an independent patient cohort.

Aspirin- and non-steroidal anti-inflammatory drug (NSAID)-induced apoptosis is one of the important mechanisms for their anti-tumour effect in gastric cancer. We aimed at determining the role of bcl-2 family proteins and caspases in the apoptotic process. Gastric cancer cell lines AGS (wild-type p53) and MKN-28 (mutant p53) were used. Cell proliferation was measured by MTT assay. Apoptosis was determined by acridine orange staining. Protein expressions were determined by western blotting. Aspirin and indomethacin inhibited cell proliferation and induced apoptosis in both cells. AGS cells were more sensitive compared with MKN-28 cells. The pro-apoptotic proteins bax and bak were overexpressed after treatment, while the protein level of bcl-2 remained unchanged. Apoptosis was accompanied by an increase in caspase-3 activity and cleavage of caspase-3 and poly(ADP-ribose) polymerase. Inhibition of caspase-3 rescued aspirin-induced apoptosis. Our results suggest that one of the major pathways which mediates the anti-tumour response of aspirin and indomethacin in gastric cancer cells is through up-regulation of bax and bak and activation of caspase-3. Bax and bak are important in the chemoprevention of gastric cancer.