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Switching mechanism from AR to EGFR signaling via 3-O-sulfated heparan sulfate in castration-resistant prostate cancer

ABSTRACT: Switching mechanism from AR to EGFR signaling via 3-O-sulfated heparan sulfate in castration-resistant prostate cancer

PROVIDER: PRJNA926489 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23191178.fastq.gz	Fastqsanger.gz
	SRR23191179.fastq.gz	Fastqsanger.gz
	SRR23191180.fastq.gz	Fastqsanger.gz
	SRR23191181.fastq.gz	Fastqsanger.gz
	SRR23191182.fastq.gz	Fastqsanger.gz

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Similar Datasets

Switching mechanism from AR to EGFR signaling via 3-O-sulfated heparan sulfate in castration-resistant prostate cancer

Project description:Expression of HS3ST1 is markedly upregulated in castration-resistant prostate cancer, which proliferates hormone-independently. In a novel mechanism, EGFR–ERK1/2 signaling is activated via 3-O-sulfated HS and EGF/HB-EGF binding in castration-resistant prostate cancer.

2023-07-20 | GSE223471 | GEO

Switching mechanism from AR to EGFR signaling via 3-O-sulfated heparan sulfate in castration-resistant prostate cancer.

Project description:Androgen deprivation therapy is given to suppress prostate cancer growth; however, some cells continue to grow hormone-independently as castration-resistant prostate cancer (CRPC). Sulfated glycosaminoglycans promote ligand binding to receptors as co-receptors, but their role in CRPC remains unknown. Using the human prostate cancer cell line C4-2, which can proliferate in hormone-dependent and hormone-independent conditions, we found that epidermal growth factor (EGF)-activated EGFR-ERK1/2 signaling via 3-O-sulfated heparan sulfate (HS) produced by HS 3-O-sulfotransferase 1 (HS3ST1) is activated in C4-2 cells under hormone depletion. Knockdown of HS3ST1 in C4-2 cells suppressed hormone-independent growth, and inhibited both EGF binding to the cell surface and activation of EGFR-ERK1/2 signaling. Gefitinib, an EGFR inhibitor, significantly suppressed C4-2 cell proliferation and growth of a xenografted C4-2 tumor in castrated mouse. Collectively, our study has revealed a mechanism by which cancer cells switch to hormone-independent growth and identified the key regulator as 3-O-sulfated HS.

| S-EPMC10354070 | biostudies-literature

Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation [male]

Project description:FGF signaling is essential for salivary gland (SG) development and heparan sulfate (HS) regulation of FGFR function is determined by immense structural diversity of sulfated HS domains. The basement membrane (BM), containing HS proteoglycans, collagens and laminins, separates epithelia from stroma and controls growth factor-matrix cross-talk. 3-O-sulfotransferases generate highly 3-O-sulfated HS domains (3-O-HS) and Hs3st3a1 and Hs3st3b1 are enriched in myoepithelial cells (MECs), which produce BM and are a growth factor signaling hub. To investigate 3-O-HS regulation of MEC function and growth factor signaling, we generated Hs3st3a1;Hs3st3b1 double knockout (DKO) mice. The DKO HS loses specific highly 3-O-sulfated tetrasaccharides, which increases FGF/FGFR-complex binding to HS. During development this leads to increased FGFR-, BM- and MEC-related gene expression. However, in adult DKO SGs the secretory units containing acinar and MECs, have reduced MECs, increased BM and disrupted acinar polarity, resulting in salivary hypofunction. We used defined 3-O-sulfated-HS in FGFR pulldown assays and primary organ cultures to investigate 3-O-HS-dependent mechanisms regulating MEC development. We find that 3-O-HS modulates FGFR signaling to regulate MEC BM synthesis which is critical for secretory unit homeostasis and acinar function. Understanding how sulfated HS regulates development will inform the use of HS mimetics in organ regeneration.

2024-08-02 | GSE235184 | GEO

Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation [female]

2024-08-02 | GSE235185 | GEO

A genome-wide CRISPR/Cas9 screen reveals KDM2B as a modifier of protein binding to heparan sulfate

Project description:Heparan sulfate proteoglycans (HSPGs) are expressed on virtually all animal cells and are involved in many important biological processes. Each HSPG consists of a core protein with one or more covalently attached linear heparan sulfate (HS) chains composed of alternating glucosamine and uronic acids that are heterogeneously N- and O-sulfated. The arrangement and orientation of the sulfated sugar residues of HS specify the location of distinct ligand binding sites on the cell surface, and these modifications can vary temporally during development and spatially across tissues. While most of the enzymes involved in HS biosynthesis have been studied extensively, much less information exists regarding the specific mechanisms that give rise to the variable composition and binding properties of HS.

2021-01-28 | GSE163162 | GEO

A genome-wide CRISPR/Cas9 screen reveals KDM2B as a modifier of protein binding to heparan sulfate

2021-01-28 | GSE145789 | GEO

Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation

Project description:Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation

| PRJNA984724 | ENA

Protein interactors of 3-O sulfated heparan sulfates in human MCI and age-matched control cerebrospinal fluid

Project description:Heparan (HS) proteoglycans (HSPGs) are common on the cell surface and mediate many physiological processes. Binding of HSPG ligands is determined by the sulfation code on the heparan sulfate chain and the HS chain can be N-/2-O/6-O- or 3-O-sulfated, generating a heterogenous sulfation pattern. 3-O sulfated HS (3S-HS) have been reported to play a role in several pathological processes such as the coagulation system, viral pathogenesis, or in the binding and internalization of tau in Alzheimer’s disease. Few 3S-HS-specific interactors are known and the role of 3S-HS in health and disease is limited, especially in the central nervous system. Using human CSF as a surrogate for the extracellular compartment of the CNS, we determined the interactome of synthetic heparan sulfate oligosaccharides with defined sulfation patterns. These AE-MS studies significantly expand the proteins that can interact with HS and for which 3O sulfation is required. LRP1 was found as a novel 3S-HS interactor, requiring GlcA-GlcNS6S3S for binding, similar to ATIII. Both interactions were validated via Western blot. Our dataset brings forward new HS and 3S-HS ligands which can be pertinent to unravel molecular mechanisms dependent on 3S-HS in (patho)physiological conditions.

2022-08-09 | PXD034935 | Pride

Heparan sulfate in skin wounds

Project description:Standardized skin wounds were established surgically on mice and allowed to heal during a 15-day period. Expression of genes related to heparan sulfate biosynthesis was studied in wound bed and edges during the healing process. Keywords: Time course

2008-04-01 | GSE7435 | GEO

Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation [male]

Project description:Specific 3-O-sulfated heparan sulfate domains regulate salivary gland basement membrane metabolism and epithelial differentiation [male]

| PRJNA984728 | ENA

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