STAT3-induced upregulation of lncRNA SNHG17 predicts a poor prognosis of melanoma and promotes cell proliferation and metastasis through regulating PI3K-AKT pathway.
IMPLICATIONS: This study suggests that AKT1<sup>E17K</sup> promotes melanoma brain metastasis through activation of FAK and provides a rationale for the therapeutic targeting of AKT and/or FAK to reduce melanoma metastasis.
Furthermore, the results showed that the mRNA and protein expression levels of AKT1 were downregulated in the melanoma cell lines when miR429 was overexpressed according to qRT-PCR and western bolt, indicating MicroRNA-429 may directly target AKT1 in melanoma.
In conclusion, these results revealed that bufadienolides effectively induced apoptosis and autophagy in A‑375 cells via the AKT pathway, and therefore may be one of the candidate targets for the future development of targeted drugs to treat melanoma.
We observed that melanoma PDXs resistant to CDK4/6i frequently displayed activation of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, and inhibition of this pathway improved CDK4/6i response in a p21-dependent manner.
The presence of a BRAF V600E mutation and activation of ERK, MEK, S6, and AKT were assessed with immunohistochemistry in 35 conjunctival nevi and 31 melanomas.
Significantly, ZnO NPs inhibit extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) associated with melanoma progression, drug resistance, and metastasis.
Immune checkpoint and serine/threonine-protein kinase inhibitors have become a standard of care for advanced cutaneous melanoma, but dacarbazine-based chemotherapies are occasionally used.
We propose that cotreatment increased ROS-induced cell cycle arrest and cellular apoptosis and inhibits melanoma growth by regulating the AKT-Nrf2 pathway in A375 cells which offers a possible therapeutic intervention strategy for the treatment of human melanoma.
Furthermore, we found that RGS1 may promote melanoma progression through the downstream effects of Gαs signaling, such as the increased phosphorylation of AKT and ERK by western blotting.
Moreover, acquired resistance to BRAF inhibitors in melanoma is dependent on dynamic regulation of KRAS expression with subsequent AKT and extracellular-signal regulated kinase activation and can be overcome by KRASi.
Moreover, we identified AXL as a key upstream effector of AKT pathway-associated resistance to BRAFi in melanoma with wildtype PTEN, but not in melanoma with impaired PTEN.
Melanoma specific killing was in the order; ZnO > B4C ≥ Cu > MgO > Co3O4 > Fe2O3 > NiO, ZnO-NP inhibiting B16F10 and A375 cells as well as ERK enzyme (>90%) and several other cancer-associated kinases (AKT, CREB, p70S6K).
This review discusses the role MAPK and Phosphatidylinositol-3-kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathways play in the mechanism of resistance of melanomas.
Identification of mutations in the gene encoding the serine/threonine-protein kinase, BRAF, and constitutive activation of the mitogen-activated protein kinase (MAPK) pathway in around 50% of malignant melanomas have led to the development and regulatory approval of targeted pathway inhibitor drugs.