Targeting AXL can effectively overcome c-Met-induced therapeutic resistance in renal cancer and promote tumor cell death through increased oxidative stress.

The mechanisms underlying therapeutic resistance to c-Met/receptor tyrosine kinase (RTK) inhibitors in renal cancer remain unexplored. In renal cell carcinoma (RCC) cells, both AXL and c-Met are highly upregulated. Notably, we found that prolonged treatment with the c-Met/RTK inhibitor, cabozantinib (Cabo), a standard treatment for advanced-stage RCC, markedly increased total c-Met levels and promoted renal cancer cell proliferation.

AXL signaling in cancer: from molecular insights to targeted therapies.

AXL, a member of the TAM receptor family, has emerged as a potential target for advanced-stage human malignancies. It is frequently overexpressed in different cancers and plays a significant role in various tumor-promoting pathways, including cancer cell proliferation, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, stemness, DNA damage response, acquired therapeutic resistance, immunosuppression, and inflammatory responses. Beyond oncology, AXL also facilitates viral infections, including SARS-CoV-2 and Zika highlighting its importance in both cancer and virology.

Recent developments in receptor tyrosine kinase inhibitors: A promising mainstay in targeted cancer therapy.

During the past two decades, significant advances have been made in the discovery and development of targeted inhibitors aimed at improving the survival rates of cancer patients. Among the multitude of potential therapeutic targets identified thus far, Receptor Tyrosine Kinases (RTKs) are of particular importance. Dysregulation of RTKs has been implicated in numerous human diseases, particularly cancer, where aberrant signaling pathways contribute to disease progression.

Aminoacyl-tRNA synthetase - a molecular multitasker.

Aminoacyl-tRNA synthetases (AaRSs) are valuable "housekeeping" enzymes that ensure the accurate transmission of genetic information in living cells, where they aminoacylated tRNA molecules with their cognate amino acid and provide substrates for protein biosynthesis. In addition to their translational or canonical function, they contribute to nontranslational/moonlighting functions, which are mediated by the presence of other domains on the proteins. This was supported by several reports which claim that AaRS has a significant role in gene transcription, apoptosis, translation, and RNA splicing regulation.

Investigation of Resistance Genes in Genus Reveals Highly Variable NLRome in Parallel Domesticated Member Species.

is a unique genus that consist of multiple crop species that are domesticated in parallel fashion between 7-10 thousand years ago. Here we studied the evolution of nucleotide-binding site leucine-rich repeat receptor (NLR) genes across five crop species of genus . In total identified 286, 350, 234, 250, 108 and 161 NLR genes were from , , , , and respectively.

Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair.

Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo.

Genome-wide DNA hypermethylation opposes healing in patients with chronic wounds by impairing epithelial-mesenchymal transition.

An extreme chronic wound tissue microenvironment causes epigenetic gene silencing. An unbiased whole-genome methylome was studied in the wound-edge tissue of patients with chronic wounds. A total of 4,689 differentially methylated regions (DMRs) were identified in chronic wound-edge skin compared with unwounded human skin.

Cutaneous Epithelial to Mesenchymal Transition Activator ZEB1 Regulates Wound Angiogenesis and Closure in a Glycemic Status-Dependent Manner.

Epithelial to mesenchymal transition (EMT) and wound vascularization are two critical interrelated processes that enable cutaneous wound healing. Zinc finger E-box binding homeobox 1 (ZEB1), primarily studied in the context of tumor biology, is a potent EMT activator. ZEB1 is also known to contribute to endothelial cell survival as well as stimulate tumor angiogenesis.

Polycomb complex mediated epigenetic reprogramming alters TGF-β signaling via a novel EZH2/miR-490/TGIF2 axis thereby inducing migration and EMT potential in glioblastomas.

Recent advancement in understanding cancer etiology has highlighted epigenetic deregulation as an important phenomenon leading to poor prognosis in glioblastoma (GBM). Polycomb repressive complex 2 (PRC2) is one such important epigenetic modifier reportedly altered in GBM. However, its defined mechanism in tumorigenesis still remains elusive.

Fisetin suppresses migration, invasion and stem-cell-like phenotype of human non-small cell lung carcinoma cells via attenuation of epithelial to mesenchymal transition.

Fisetin (3,3',4',7-tetrahydroxyflavone) is a bioactive polyphenolic flavonoid found in many fruits and vegetables. It exhibits a variety of pharmacological activities including anticancer and anti-invasive effects. Epithelial to mesenchymal transition (EMT) allows the tumor cells to acquire increased migratory and invasive properties mediating their dissemination to faraway sites, thus favoring metastasis.

Berberine in combination with doxorubicin suppresses growth of murine melanoma B16F10 cells in culture and xenograft.

Melanoma is very aggressive and major cause of mortality due to skin cancer. Herein, we studied the anticancer effects of berberine, a plant alkaloid, in combination with doxorubicin on murine melanoma B16F10 cells in vitro and in vivo. This drug combination strongly inhibited cell growth and induced cell death, and caused G2/M arrest in cell cycle together with a decrease in Kip1/p27.