Biology subjects

Amoresano, A.

Publications and source records attributed to Amoresano, A..

3 recordsLinked to original sources

bioRxiv2025

Type 1 LacNAc and LacdiNAc on N-glycans as molecular biomarkers of human melanoma cells

Melanoma, the most dangerous form of skin cancer, is characterized by its high potential to spread or metastasize. Tumor progression is associated with changes in glycosylation that occur early in carcinogenesis and evolve as the cancer develops and spreads. To identify new melanoma transformation markers, we analyzed N-glycans from melanocytes and melanoma cell lines at different progression stages. We performed analyses using matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) and hydrophilic interaction liquid chromatography (HILIC)-high performance liquid chromatography (HPLC) techniques on N-glycans without and after digestion with exoglycosidase arrays. Our results showed that, unlike melanocytes, melanoma cells express higher levels of type 1 LacNAc units and triantennary complex type glycans instead of high-mannose type glycans. Our results revealed that the N-glycomes of all analyzed cell lines possess Lewis X/A epitopes and, for the first time, demonstrate the presence of Gal{beta}1-4Gal{beta}1-4GlcNAc and Gal{beta}1-3Gal{beta}1-3GlcNAc units. The characteristic feature of melanoma cells is the presence of LacdiNAc structures. Our study provides the first comprehensive characterization of the N-glycome of melanocytes and suggests novel glyco-biomarkers of melanoma progression.

cancer biology↗

bioRxiv2021

Tomato Prosystemin is much more than a simple Systemin precursor

Systemin (Sys) is an octadecapeptide which, upon wounding, is released from the carboxy terminus of its precursor, prosystemin(ProSys) to promote plant defenses. Recent findings on the disordered structure of ProSysprompted us to investigate a putative biological role of the whole precursor deprived of Sys peptide. We produced transgenic tomato plants expressing a truncated ProSys gene in which the exon coding for Sys was removed and compared their defense response with that induced by the exogenous application of the recombinant deleted ProSys[ProSys(1-178)].By combining protein structure analyses, transcriptomic analysis, gene expression profiling and bioassays with different pests we demonstrate that the truncated ProSys, that does not induce the endogenous ProSys gene, promotes defense barriers in tomato plants through a hormone independent defense pathway, likely associated with the production of oligogalacturonides (OGs). Both transgenic and plants treated with the recombinant protein showed the modulation of the expression of genes linked with defense responses and resulted protected against the lepidopteran pest Spodoptera littoralis and the fungus Botrytis cinerea. Our results suggest that the overall function of the wild type prosystemin is more complex than previously shown as it might activate at least two tomato defense pathways: the well-known Sys-dependent pathway connected with the induction of JA biosynthesis and the successive activation of a set of defense-related genes and the ProSys(1-178)-dependent pathway associated with OGs production leading to the OGs mediate plant immunity.

genetics↗

bioRxiv2019

Synthetic lethality screening reveals FDA-approved drugs that overcome ATP7B-mediated tolerance of tumor cells to cisplatin

Tumor resistance to chemotherapy represents an important challenge in modern oncology. Although platinum (Pt)-based drugs have demonstrated excellent therapeutic potential, their effectiveness in a wide range of tumors is limited by the development of resistance mechanisms. One of these mechanisms includes increased cisplatin sequestration/efflux by the copper-transporting ATPase, ATP7B. However, targeting ATP7B to reduce Pt tolerance in tumors could represent a serious risk because suppression of ATP7B might compromise copper homeostasis, as happens in Wilson disease.\n\nTo circumvent ATP7B-mediated Pt tolerance we employed a high-throughput screen (HTS) of an FDA/EMA-approved drug library to detect safe therapeutic molecules that promote cisplatin toxicity in the resistant ovarian carcinoma cell line IGROV-CP20. Using a synthetic lethality approach we identified and validated three hits (Tranilast, Telmisartan and Amphotericin B) that could reduce cisplatin resistance. All three drugs induced Pt-mediated DNA damage and inhibited either expression or trafficking of ATP7B in a tumor-specific manner. Global transcriptome analyses showed that Tranilast and Amphotericin B affect expression of genes operating in several pathways that confer tolerance to cisplatin. In the case of Tranilast, these included key molecular players operating in the distribution of platinum to different intracellular compartments. In particular, Tranilast was found to suppress ATOX1 and, as a consequence, ATOX1-mediated trafficking of ATP7B in response to cisplatin.\n\nConsidering the well-known safety profiles of Tranilast, Telmisartan and Amphotericin B, these drugs emerge as potential candidates that might be used for the rapid development of new therapeutic strategies to overcome resistance of tumors to Pt-based chemotherapy.

cancer biology↗