BMX (BMX Non-Receptor Tyrosine Kinase)

Critically, the STAT3 inhibitor S3I-201 abrogated the pro-tumorigenic effects of BMX overexpression on HT29 cell proliferation, migration, and invasion. In conclusion, our findings establish that BMX drives CRC progression by activating STAT3 signaling pathway, which subsequently suppresses E-cadherin expression to induce EMT.

This study serves as proof-of-principle for this therapeutic strategy but also highlights the urgent need for more specific molecules to inhibit BMX kinase activity. Created with BioRender.com.

Profoundly, the novel LNPs showed significant in-vivo anticancer activity in the Castration-Resistant Prostate Cancer (CRPC) animal model compared to control or the Onpattro-like formulation. The results from this study further support the promise of such novel LNPs in cancer therapeutics development.

AlphaScreen of a compound library identifies NSC617570 as an efficient inhibitor of PRKCQ-AS1 RNA and MSI2 protein interaction, and NSC617570 reduces BMX expression, ERK protein phosphorylation, neuroblastoma cell proliferation in vitro and tumor progression in mice. The study demonstrates that PRKCQ-AS1 RNA interacts with MSI2 protein to induce neuroblastoma tumorigenesis, and that targeting PRKCQ-AS1 and MSI2 interaction with small molecule compounds is an effective anticancer strategy.

Our study revealed BMX as a diagnostic biomarker in BRCA, COAD, LUAD, LUSC, and READ and a prognostic biomarker in KIRC, LIHC, SARC, and UCEC. Furthermore, epigenetic variables may have a greater impact on BMX expression levels especially in LUAD and LUSC. This study also emphasized the role of BMX in the infiltration of immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, in certain cancers. The BMX expression level highlights the prognostic value and potential therapeutic potential of BMX.

Finally, BMX inhibitors readily reversed this cellular state, increased the sensitivity of NB spheroids toward chemotherapy, and partially reduced tumor growth in a preclinical NB model. Altogether, our study identifies BMX as a promising innovative therapeutic target for patients with high-risk MYCN nonamplified NB.