Biology subjects

Carlevaris, O.

Publications and source records attributed to Carlevaris, O..

3 recordsLinked to original sources

bioRxiv2025

Transcription factor 19 is an androgen responsive gene that modulates vessel homeostasis and sustains metastatic prostate cancer

Prostate cancer is a prevalent tumor type that, despite being highly curable, progresses to metastatic disease in a fraction of patients, thus accounting for more than 350.000 annual deaths worldwide. In turn, uncovering the molecular insights of metastatic disease is instrumental to improve the survival rate of prostate cancer patients. By means of gene expression metanalysis in multiple prostate cancer patient cohorts, we identified a set of genes that are differentially expressed in aggressive prostate cancer. Transcription factor 19 (TCF19) stood out as an unprecedented epithelial gene upregulated in metastatic disease, with prognostic potential and associated with the activity of androgen receptor. By combining computational and empiric approaches, our data revealed that TCF19 is required for full metastatic capacity and its depletion influences core cancer-related processes, such as vascular permeability, supporting the role of this gene in the dissemination of prostate tumor cells.

cancer biology↗

bioRxiv2024

The transcriptional landscape of metastatic hormone-naive prostate cancer

Metastatic hormone-naive prostate cancer (mHNPC) is an infrequent form of this tumour type that is characterized by metastasis at the time of diagnosis and accounts for 50% of prostate cancer-related deaths. Despite the extensive characterization of localized and metastatic castration resistant prostate cancer (mCRPC), the molecular characteristics of mHNPC remain largely unexplored. Here we provide the first extensive transcriptomics characterization of mHNPC. We generated discovery and validation bulk and single-cell RNA-Seq datasets and performed integrative computational analysis in combination with experimental studies. Our results provide unprecedented evidence of the distinctive transcriptional profile of mHNPC and identify stroma remodelling as a predominant feature of these tumours. Importantly, we discover a central role for the transcription factor SOX11 in triggering a heterotypic communication that is associated to the acquisition of metastatic properties. Our study will constitute an invaluable resource for a profound understanding of mHNPC that can influence patient management.

cancer biology↗

bioRxiv2020

USP29 is a novel non-canonical Hypoxia Inducible Factor-α activator

Hypoxia Inducible Factor (HIF) is the master transcriptional regulator that orchestrates cellular adaptation to low oxygen. HIF is tightly regulated via the stability of its -subunit, which is subjected to oxygen-dependent proline hydroxylation by Prolyl-Hydroxylase Domain containing proteins (PHDs/EGLNs), and ultimately targeted for proteasomal degradation through poly-ubiquitination by von-Hippel-Lindau protein (pVHL). However, sustained HIF- signalling is found in many tumours independently of oxygen availability pointing towards the relevance of non-canonical HIF- regulators. In this study, we establish the Ubiquitin Specific Protease 29 (USP29) as direct post-translational activator of HIF- in a variety of cancer cell lines. USP29 binds to HIF-, decreases poly-ubiquitination and thus protects HIF- from proteasomal degradation. Deubiquitinating activity of USP29 is essential to stabilise not only HIF-1 but also HIF-2, via their C-termini in an oxygen/PHD/pVHL-independent manner. Furthermore, in prostate cancer samples the expression of USP29 correlates with the HIF-target gene CA9 (carbonic anhydrase 9) as well as disease progression and severity.

cell biology↗