HOXB13 expression

Furthermore, Her2 suppresses the transcription of MAP3K4 by downregulating the expression of HOXB13, a crucial transcription factor contributing to MAP3K4 expression in DCIS cells. Together, these findings unveil a novel downstream regulatory mechanism through which Her2 inhibits the activation of p38 signaling and facilitates early dissemination of breast cancer, offering insights into the development of effective diagnostic methods and targeted therapies for inhibiting the early dissemination of Her2 + breast cancer.

HOXB13 is frequently co-gained with ERBB2 at both low-copy number level or as complex high-level amplification with relative BRCA1 loss. ERBB2/HOXB13 amplified, BRCA1-lost tumors are strongly enriched in breast cancer, and patients with such breast tumors experience a shortened PFS.

Finally, we confirmed that METTL14-modified HOXB13 exerted an oncogenic effect through activation of the nuclear factor kappa B (NF-κB) pathway. In conclusion, our data demonstrated that the m6A modification of HOXB13, mediated by METTL14, facilitated the advancement of CC through targeting the NF-κB pathway, which may be a potential molecular target for the treatment of CC.

© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

PSMA-targeted therapies are rapidly advancing, but their efficacy is strongly limited by the heterogeneous expression of the target. A thorough comprehension of how PSMA is regulated will help improve the outcomes through increasing PSMA expression and will provide the basis for synergistic combination therapies.

The homozygous adrenal-permissive HSD3B1 variant (c.1100 CC) is associated with distinct tumoral features characterized by elevated AR signaling and MAPK activation. It is also associated with a unique immune-cell regulatory landscape, with higher B7-H3 expression, increased intratumoral dendritic cells and decreased immunosuppressive neutrophils. This distinct molecular landscape of HSD3B1 c.1100 CC–associated prostate cancers warrants special therapeutic considerations, including possibly using B7-H3–targeted therapies.

Furthermore, our findings support the utility of HOXB13 as a diagnostic biomarker for prostate cancer, particularly to confirm the prostatic origin of advanced metastatic castration-resistant tumors.

A comprehensive and comparative analysis of mRNA expression levels and methylation patterns between TCGA breast cancer samples with high and low expression of HOXB13 revealed key signaling pathways and biological processes that may provide insights on the molecular mechanism of HOXB13 in the regulation of response to endocrine therapy in HR+ breast cancer.

Furthermore, the study revealed associations between CKD stages and prognostic grade groups in different molecular subtypes, pointing out an intricate interplay between renal function and tumor behavior. Although the molecular classification of prostate acinar ADK is not yet implemented, this research underscores the variability of renal function parameters in different molecular subtypes, offering potential insights into patient prognosis.

Both HOXA13 and HOXB13 protein expression were found to be associated with bladder tumorigenesis. The putative oncogenic and tumor suppressive roles of HOXA13 and HOXB13, respectively, suggest their potential utility as biomarkers in bladder cancer.

This work uncovers a previously unanticipated molecular cascade by which mTOR directly phosphorylates HOXB13 to dictate a specific gene program with oncogenic implications in prostate cancer. Implications: Control of HOXB13 transcriptional activity via its direct phosphorylation by the mTOR kinase is a potential therapeutic avenue for the management of advanced prostate cancer.

Higher CTC HOXB13 expression is associated with AR dependent biomarkers in CTCs and is adversely prognostic in the context of potent AR inhibition in men with mCRPC, and this assay could be useful to select for patients appropriate for AR or future HOXB13 targeted therapies. Clinical trial information: NCT02269982.