ETV5 (ETS Variant Transcription Factor 5)

Therapeutically, ETV5 ablation synergized with anti-PD-L1 therapy to enhance tumor control, mirroring clinical observations where high ETV5 expression predicted immunotherapy resistance. Our study uncovers a non-canonical, transcription-independent role of ETV5 in orchestrating the JAK2/STAT3/CCL2 axis to sustain PMN-MDSC-mediated immune evasion, proposing ETV5 as a druggable target to overcome ICI resistance in solid tumors.

This study delineates the mechanism that TREM2+ TAMs promote LN metastasis in HNSCC by facilitating CD8+ T cells exhaustion via SPP1-CD44-BHLHE40 axis, proposing TREM2+ TAMs as potential therapeutic target for HNSCC.

Using high-throughput screening, we established that combining p38 inhibitors with the BRAF inhibitor dabrafenib showed strong synergy in vitro, including in cells resistant to dabrafenib and trametinib that had acquired a secondary TP53 mutation. Overall, our findings suggest an oncogenic link between the MAPK and p38/MAPK14 pathways and that combining p38 pathway inhibitors with dabrafenib-targeted therapy could improve treatment outcomes for aggressive thyroid cancers. However, more specific and effective p38 inhibitors are required to fully harness this potential.

Our findings identify ETV4 as a key transcriptional regulator of immune evasion in melanoma by controlling PD-L1 expression. ETV4 may act as a predictive biomarker for immunotherapy outcomes.

Regulatory network analysis revealed that the transcription factors ETV5, IRF5, IRF7, RORB, RORC, and SMAD1 drive inflammatory and profibrotic signatures via the IL-17, JAK-STAT, and TGF-β pathways. This study identifies monocytes as central orchestrators of immune dysregulation in ASS-ILD, highlighting IFN/TNF signaling and associated transcriptional regulators as therapeutic targets.

Unlike the other NPs, the GRP1 and GRP2 NPs upregulated expression of genes for proteins involved in immune function. The present work will serve as an important resource for investigators interested in further defining the transit amplifying progenitors of the mammalian SVZ.

Our study revealed that ETV5 induces cell proliferation, invasion and migration by upregulating LGR4 in NPC. ETV5/LGR4 signaling may serve as a therapeutic target for NPC patients.

AKT-mediated degradation of FOXO1 and subsequent loss of the ERG/PRC2 interaction provides a mechanism for ERG synergy with PTEN deletion in prostate cancer. Implications: These findings indicate that ETS transcription factors that drive prostate cancer and Ewing sarcoma utilize similar mechanisms and thus could be targeted by similar therapeutic approaches.

Indeed, the deletion of pro-survival BCL2A1 re-sensitized COP1 mutant cells to vemurafenib treatment. These observations indicate that the post-translational regulation of ETV5 by CRL4COP1/DET1 modulates transcriptional outputs in ERK-dependent cancers, and its inactivation contributes to therapeutic resistance.

Trial Registration: Registry and the Registration N° of the study/trial: 12TETE01, ID-RCB No. 2012-A00585-38, approval Date: May 7, 2012.

Investigation of functional significances of ETS variant transcription factor 5 (ETV5) expression in the pancreatic cancer cells revealed that ETV5 was associated with resistance to gemcitabine; while no significance in proliferation, migration, and invasion. ETV5 expression in pancreatic ductal adenocarcinoma tissues resected from patients undergoing neoadjuvant chemotherapy was associated with KRAS mutations, which was consistent with ETV5 as a downstream upregulated molecule of RAS-ERK1/2 pathway. This study elucidated the mechanism of ERK1/2-mediated transcriptional regulation of ETV5 in human cancer cells, which could contribute to understand pancreatic cancer pathobiology.