VGLL4 (Vestigial Like Family Member 4)

Instead of keratocystoma being defined narrowly by IRF2BP2::RUNX2 fusions, there may exist a broader spectrum of RUNX1/2-rearranged cystic, squamous salivary gland tumors. More cases will be needed to further define this emerging family of neoplasms.

Our findings suggest that osteosarcoma can rarely present with FOS gene fusions and be associated with an indolent progression, challenging the specificity of such signatures for osteoblastoma diagnosis. This discovery also raises the hypothesis of malignant transformation from osteoblastoma to osteosarcoma and underscores the necessity for diligent monitoring of FOS-rearranged bone-forming tumors for optimal therapeutic management.

Our observations shed light on the potential molecular mechanisms by which exercise influences cancer development and provide insights into novel therapeutic strategies targeting these pathways.

Moreover, EIF4A3 has binding sites in the upstream region of the GNAI2 pre-mRNA, and we confirmed that circGNAI2 was downregulated by EIF4A3 in TNBC cells. Overall, our study indicates that EIF4A3-regulated circGNAI2 suppresses TNBC progression possibly by regulating the miR-454-3p/VGLL4/STAT3 pathway, providing pivotal potential therapeutic targets for the treatment of TNBC.

Our data reveal a category of TEAD inhibitors that act as "molecular glues" toward the repressive VGLL4-TEAD interaction. These findings open up understandings for curbing the oncogenic activity of Hippo pathway deregulation in cancer, and identify glue-like molecules that promote transcriptional repression.

Finally, in vivo inhibition of lnc-536 using GapmeRs in Sugen-hypoxia and HIV-transgenic pulmonary hypertension rats prevented the increase in right ventricular systolic pressure, right ventricular hypertrophy/fibrosis, and pulmonary vascular remodeling with a parallel increase in HOXB13 expression in rat PASMCs. Lnc-536 acts as a decoy for RBM25, which in turn sequesters SFPQ, leading to a decrease in HOXB13 expression and hyperproliferation of smooth muscle cells by potentially regulating Wnt and Hippo signaling associated with PAH development.

Targeting nuclear E3 ligases in multiple types of patient-derived tumor organoids suppressed their expansion. Our identification of UBR5 as the bona fide E3 ligase of VGLL4 offers a molecular framework of nuclear Hippo-YAP regulation and suggests nuclear ubiquitination as a potential therapeutic target for YAP-dependent malignancies.

Prior studies indicate a pro-tumorigenic role for this protein in several cancers including carcinoma of the breast. This review aims at summarizing our present knowledge about the functions of VGLL1, and the mechanisms that regulate its expression in cancer.

The results suggest distinct roles for AIFM3, VGLL4, and WNT4 in CRC progression, highlighting only VGLL4 as a potential prognostic marker. Further evaluation of VGLL4 and its specific role in CRC progression remains to be elucidated.

Structural differences in YAP1 and TAZ TBDs were also identified, which may contribute to the distinct binding of these proteins to TEAD. Our findings expand our understanding of TEAD regulation and highlight the potential of an optimized TEADi as a more potent, specific, and versatile tool for studying TEAD-transcriptional activity.

In vitro, overexpression of VGLL4 resulted in the downregulation of YAP activity in benign NF2 mutant meningioma cells, confirming the direct link between VGLL4 expression and decreased levels of YAP activity observed in aggressive NF2 mutant meningiomas. Our results shed new insight into the biology of benign and aggressive NF2 mutant meningiomas and may have important implications for the efficacy of therapies targeting oncogenic YAP1 activity in NF2 mutant meningiomas.