Biology subjects

Kalisz, M.

Publications and source records attributed to Kalisz, M..

3 recordsLinked to original sources

bioRxiv2026

Nerve growth factor receptor identifies a basal subpopulation linked to poor prognosis and reduced immunotherapy responses in bladder cancer

PurposeBladder cancer (BLCA) is a heterogeneous tumor type. Only one third of muscle-invasive (MIBC) patients respond to immune checkpoint inhibitors (ICIs). Reliable resistance markers are needed to guide clinical decisions. We investigated the nerve growth factor receptor (NGFR) in BLCA and analyzed its correlation with disease progression and response to immunotherapy. Experimental DesignWe analyzed NGFR expression in BLCA cell lines, organoids, mouse models and patient samples. The cohorts used were The Cancer Genome Atlas (TCGA), enriched in muscle-invasive bladder cancer (MIBC) (n=407); IMvigor210, representing MIBC patients treated with ICIs (n=348); and UROMOL2, as a non-muscle-invasive bladder cancer (NMIBC)-specific cohort (n=535). IMvigor010 was also included (n=728). Patients were stratified by NGFR expression quartiles. We analyzed survival and tumor subtypes and performed stromal deconvolution and functional profiling. We assessed stemness- and invasion-related features in SCaBER cells. ResultsNGFR marks a basal tumor cell subcluster and is independently associated with poor prognosis in TCGA and IMvigor210. NGFR-high tumors show stromal content enriched in cancer-associated fibroblasts, lower neoantigen burden, higher CD8+ T effector signature together with an immune-excluded phenotype, and a CAF-specific TGF{beta} signature. In the immunotherapy-treated cohort, high NGFR expression was also associated with poorer outcome. Functionally, NGFR appears to promote a stem-like/pro-invasive program in BLCA cells. ConclusionsNGFR identifies a basal-like BLCA subpopulation linked to poor survival, while its association with immunotherapy response requires further validation. In addition, our in vitro analyses support a role of NGFR in stem-like and invasive traits, highlighting its relevance as a biomarker in BLCA.

cancer biology↗

bioRxiv2025

STAG2 cohesin cooperates with DREAM to maintain quiescence and suppress tumourigenesis in the urothelium

The maintenance of quiescence is essential for tissue homeostasis. STAG2 is one of the few genes mutated in the normal urothelium of organ donors, with mutant cells undergoing positive selection 1. STAG2 is also a major tumour suppressor gene 2-4 and its inactivation is an early event in bladder carcinogenesis 1,3. However, how STAG2, a cohesin component, regulates urothelial homeostasis remains largely unknown. Here, we demonstrate that Stag2 inactivation in normal murine urothelial cells interferes with differentiation programs, triggers transient cell cycle entry, and primes cells for clonal expansion under stress. Moreover, STAG2 loss enhances tumor formation in urothelial cells expressing mutant FGFR3 - the key oncogene in bladder cancer 5. We reveal that STAG2 cooperates with the DREAM transcriptional complex, a master regulator of quiescence 6,7, by binding to shared genomic sites, including cell cycle control genes. STAG2 loss alters DREAM target expression, complex composition, and chromatin distribution, and leads to rewiring of chromatin interactions involving DREAM binding motifs in genes critical for cell cycle entry. Our findings provide compelling evidence that STAG2 loss disrupts in 3D genome organization through a novel mechanism involving the DREAM complex, thereby impairing homeostatic quiescence and increasing oncogenic sensitivity.

cancer biology↗

bioRxiv2019

HNF1A recruits UTX to activate a differentiation program that suppresses pancreatic cancer

Defects in transcriptional regulators of pancreatic exocrine differentiation have been implicated in pancreatic tumorigenesis, but the molecular mechanisms are poorly understood. The locus encoding the transcription factor HNF1A harbors susceptibility variants for pancreatic ductal adenocarcinoma (PDAC), while KDM6A, encoding the histone demethylase UTX, carries somatic mutations in PDAC. Here, we show that pancreas-specific Hnf1a null mutations phenocopy Utx deficient mutations, and both synergize with KrasG12D to cause PDAC with sarcomatoid features. We combine genetic, epigenomic and biochemical studies to show that HNF1A recruits UTX to genomic binding sites in pancreatic acinar cells. This remodels the acinar enhancer landscape, activates a differentiation program, and indirectly suppresses oncogenic and epithelial-mesenchymal transition genes. Finally, we identify a subset of non-classical PDAC samples that exhibit the HNF1A/UTX-deficient molecular phenotype. These findings provide direct genetic evidence that HNF1A-deficiency promotes PDAC. They also connect the tumor suppressive role of UTX deficiency with a cell-specific molecular mechanism that underlies PDAC subtype definition.

genomics↗