MRTFA (Myocardin Related Transcription Factor A)

MRTF-A/SRF promotes histone H3K4me3 methylation by regulating BRG1, thereby inducing macrophage polarization toward the M2 phenotype and enhancing migratory, invasive, and angiogenic abilities of ectopic endometrial cells, ultimately contributing to EMS progression. BWHD exerts therapeutic effects in EMS by downregulating MRTF-A, attenuating MRTF-A-mediated M2 macrophage polarization, and restoring macrophage immune homeostasis.

Moreover, we found that dual therapy with CCG081 and proteasome inhibition further improved outcomes, leading to undetectable tumors in ∼20% of mice. Together, these data suggest that the MRTFA/SRF pathway is a critical regulator of quiescence in cancer and a potential therapeutic target.

The compounds, achieving IC50 values as low as 0.13 ± 0.02 μM, are over 290-fold more active in vitro than the clinical standard doxorubicin (IC50 = 38.17 ± 13.32 μM)...Additionally, these compounds reduce nuclear localization of myocardin-related transcription factor A (MRTF-A), a key driver of tumor resistance. This new study lays the groundwork for developing quinazoline-thiohydantoin-based drugs that can overcome multidrug-resistance mechanisms.

Importantly, pharmacological activation of BK channels reduced metastatic burden in mice and improved lysis of cancer cells by cytotoxic T-lymphocytes. These results highlight the unique ionic regulation of stiffness in cancer cells and point to BK channel agonism as a new therapeutic approach in cancer.

Our data indicate that Myo1f regulates monocyte adhesion and contributes to the pathogenesis of atherosclerosis by recruiting EPLINα, which stabilizes F-actin. This stabilization enhances MRTFA nuclear translocation, thereby promoting ITGB2 transcription.

This study demonstrates that INS, IGF-1, and IGF-2 regulate Rho GTPase and MRTFA activation, thereby contributing to the control of actin cytoskeletal dynamics in neuronal cells. Given the role of INS and IGFs in neuronal survival and neurodegenerative conditions, elucidating these mechanisms is of critical importance, as it offers insights into disease pathogenesis and potential therapeutic targets.

We generated DLC1 binding peptides that dissociate the MRTF-A-FLNA complex and favor the novel DLC1-FLNA complex by preventing actin polymerization and FLNA phosphorylation at serine 2152. Since FLNA phosphorylation at serine 2152 was increased in mouse xenografts, reinforcing the DLC1-FLNA complex by targeting FLNA phosphorylation at serine 2152 represents a promising therapeutic approach for HCC treatment.

Our findings suggest a role of Mrtfa in the control of morphogenetic movements during neurulation. We propose that the regulation of actomyosin contractility is an essential cellular response to Mrtfa-dependent transcriptional activation.

This study demonstrates that INS, IGF-1 and IGF-2 regulate Rho GTPase and MRTFA activation, thereby contributing to the control of actin cytoskeletal dynamics in neuronal cells. Given the role of INS and IGFs in neuronal survival and neurodegenerative conditions, elucidating the mechanisms is of critical importance, as it offers insights into disease pathogenesis and potential therapeutic targets.

Our results provide unique insights into how MRTFA and MRTFB promote metastasis in human cancer, the differences of their expression patterns, and their immune suppressive function within the breast cancer TME. Our results will guide future studies on targeting MRTFA/B transcriptional activity and the resulting immune suppression in breast cancer.

Recent studies have shown that MICAL2 is highly expressed in tumors, accelerates tumor progression, and is a novel tumor-promoting factor. This article summarizes recent research findings to review the biological functions of MICAL2, the potential mechanisms related to cancer progression, and discusses the challenges and prospects in this area, providing a new theoretical basis for clinical molecular targeted therapy for cancer.