Biology subjects

Catalano, A.

Publications and source records attributed to Catalano, A..

3 recordsLinked to original sources

bioRxiv2026

Sexually dimorphic effects of mutations in ccRCC driver genes in renal proximal tubule cells

Clear cell renal cell carcinoma (ccRCC) arises more frequently in men than in women, but it remains unclear why this is the case. Mouse models that mimic the truncal mutation of the two most commonly affected tumor suppressor genes in human ccRCC revealed that the transcriptional effects of Vhl or Vhl/Pbrm1 mutation in male and female proximal tubule cells only partially overlap. Cellular responses to mutations in these genes were also sex-specific. Vhl and Vhl/Pbrm1 mutation in females, but only Vhl/Pbrm1 mutation in males, induced the accumulation of PLIN2-coated lipid droplets. The accumulation of optically-clear lipid droplets, reflecting the hallmark clear-cell histological feature of ccRCC, only arose in Vhl/Pbrm1 mutant male mice. Consistent with lipotoxic tubular damage, markers of tubular repair and ongoing epithelial cell proliferation correlated with the lipid accumulation phenotypes. Vhl/Pbrm1 mutation caused stronger clonal expansion than Vhl mutation in males, but not in females. These findings suggest that there are likely to be sexual dimorphisms at the very earliest stages of ccRCC evolution that result from the interplay of intrinsic and mutation-induced transcriptional differences between male and female proximal tubule cells.

cancer biology↗

bioRxiv2022

Flotillin-2 regulates EGFR activation, degradation, and cancer growth

Epidermal growth factor receptor (EGFR) signaling is frequently dysregulated in various cancers. The ubiquitin ligase Cbl (Casitas B-lineage lymphoma proto-oncogene) regulates degradation of activated EGFR through ubiquitination and acts as an adaptor to recruit proteins required for trafficking. We used Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) mass spectrometry (MS) to compare Cbl complexes with or without epidermal growth factor (EGF) stimulation. We identified over a hundred novel Cbl interactors, and a secondary siRNA screen found that knockdown of Flotillin-2 (FLOT2) led to increased phosphorylation and degradation of EGFR upon EGF stimulation in HeLa cells. In PC9 and H441 cells, FLOT2 knockdown increased EGF-stimulated EGFR phosphorylation, ubiquitination, and downstream signaling, reversible by the EGFR inhibitor erlotinib. CRISPR knockout (KO) of FLOT2 in HeLa cells confirmed EGFR downregulation, increased signaling, and increased dimerization and trafficking to the early endosome. FLOT2 interacted with both Cbl and EGFR. EGFR downregulation upon FLOT2 loss was Cbl-dependent, as co-knockdown of Cbl and Cbl-b restored EGFR levels. Overexpression of FLOT2 decreased EGFR sjgnaling and growth. Overexpression of wild type (WT) FLOT2, but not the soluble G2A FLOT2 mutant, inhibited EGFR phosphorylation upon EGF stimulation in HEK293T cells. FLOT2 loss induced EGFR-dependent proliferation and anchorage-independent growth. Lastly, FLOT2 KO increased tumor formation and tumor volume in nude mice and NSG mice, respectively. These data demonstrated that FLOT2 negatively regulated EGFR activation and dimerization, as well as its subsequent ubiquitination, endosomal trafficking, and degradation, leading to reduced proliferation in vitro and in vivo.

cancer biology↗

bioRxiv2017

High-Definition Electronic Genome Maps From Single Molecule Data

With the advent of routine short-read genome sequencing has come a growing recognition of the importance of long-range, structural information in applications ranging from sequence assembly to the detection of structural variation. Here we describe the Nabsys solid-state detector capable of detecting tags on single molecules of DNA 100s of kilobases in length as they translocate through the detector at a velocity greater than 1 megabase pair per second. Sequence-specific tags are detected with a high signal-to-noise ratio. The physical distance between tags is determined after accounting for viscous drag-induced intramolecular velocity fluctuations. The accurate measurement of the physical distance between tags on each molecule and the ability of the detector to resolve distances between tags of less than 300 base-pairs enables the construction of high-density genome maps.

genomics↗