Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387263597> ?p ?o ?g. }
Showing items 1 to 68 of
68
with 100 items per page.
- W4387263597 abstract "<div>Abstract<p>High-grade serous ovarian cancer (HGSOC) is a highly aggressive and lethal subtype of ovarian cancer. While most patients initially respond to standard-of-care treatment, the majority will eventually relapse and succumb to their disease. Despite significant advances in our understanding of this disease, the mechanisms that govern the distinctions between HGSOC with good and poor prognosis remain unclear. In this study, we implemented a proteogenomic approach to analyze gene expression, proteomic and phosphoproteomic profiles of HGSOC tumor samples to identify molecular pathways that distinguish HGSOC tumors relative to clinical outcome. Our analyses identify significant upregulation of hematopoietic cell kinase (HCK) expression and signaling in poor prognostic HGSOC patient samples. Analyses of independent gene expression datasets and IHC of patient samples confirmed increased HCK signaling in tumors relative to normal fallopian or ovarian samples and demonstrated aberrant expression in tumor epithelial cells. Consistent with the association between HCK expression and tumor aggressiveness in patient samples, <i>in vitro</i> phenotypic studies showed that HCK can, in part, promote cell proliferation, colony formation, and invasive capacity of cell lines. Mechanistically, HCK mediates these phenotypes, partly through CD44 and NOTCH3-dependent signaling, and inhibiting CD44 or NOTCH3 activity, either genetically or through gamma-secretase inhibitors, can revert HCK-driven phenotypes.</p>Implications:<p>Collectively, these studies establish that HCK acts as an oncogenic driver of HGSOC through aberrant activation of CD44 and NOTCH3 signaling and identifies this network as a potential therapeutic opportunity in a subset of patients with aggressive and recurrent HGSOC.</p></div>" @default.
- W4387263597 created "2023-10-03" @default.
- W4387263597 creator A5030899790 @default.
- W4387263597 creator A5031945222 @default.
- W4387263597 creator A5052153802 @default.
- W4387263597 creator A5078684719 @default.
- W4387263597 creator A5082290950 @default.
- W4387263597 creator A5092222042 @default.
- W4387263597 date "2023-10-02" @default.
- W4387263597 modified "2023-10-03" @default.
- W4387263597 title "Data from HCK Promotes High-Grade Serous Ovarian Cancer Tumorigenesis through CD44 and NOTCH3 Signaling" @default.
- W4387263597 doi "https://doi.org/10.1158/1541-7786.c.6738452.v2" @default.
- W4387263597 hasPublicationYear "2023" @default.
- W4387263597 type Work @default.
- W4387263597 citedByCount "0" @default.
- W4387263597 crossrefType "posted-content" @default.
- W4387263597 hasAuthorship W4387263597A5030899790 @default.
- W4387263597 hasAuthorship W4387263597A5031945222 @default.
- W4387263597 hasAuthorship W4387263597A5052153802 @default.
- W4387263597 hasAuthorship W4387263597A5078684719 @default.
- W4387263597 hasAuthorship W4387263597A5082290950 @default.
- W4387263597 hasAuthorship W4387263597A5092222042 @default.
- W4387263597 hasConcept C104317684 @default.
- W4387263597 hasConcept C121608353 @default.
- W4387263597 hasConcept C126322002 @default.
- W4387263597 hasConcept C127716648 @default.
- W4387263597 hasConcept C1491633281 @default.
- W4387263597 hasConcept C150173356 @default.
- W4387263597 hasConcept C2780427987 @default.
- W4387263597 hasConcept C2780932548 @default.
- W4387263597 hasConcept C502942594 @default.
- W4387263597 hasConcept C54355233 @default.
- W4387263597 hasConcept C555283112 @default.
- W4387263597 hasConcept C62478195 @default.
- W4387263597 hasConcept C71924100 @default.
- W4387263597 hasConcept C86803240 @default.
- W4387263597 hasConcept C95444343 @default.
- W4387263597 hasConceptScore W4387263597C104317684 @default.
- W4387263597 hasConceptScore W4387263597C121608353 @default.
- W4387263597 hasConceptScore W4387263597C126322002 @default.
- W4387263597 hasConceptScore W4387263597C127716648 @default.
- W4387263597 hasConceptScore W4387263597C1491633281 @default.
- W4387263597 hasConceptScore W4387263597C150173356 @default.
- W4387263597 hasConceptScore W4387263597C2780427987 @default.
- W4387263597 hasConceptScore W4387263597C2780932548 @default.
- W4387263597 hasConceptScore W4387263597C502942594 @default.
- W4387263597 hasConceptScore W4387263597C54355233 @default.
- W4387263597 hasConceptScore W4387263597C555283112 @default.
- W4387263597 hasConceptScore W4387263597C62478195 @default.
- W4387263597 hasConceptScore W4387263597C71924100 @default.
- W4387263597 hasConceptScore W4387263597C86803240 @default.
- W4387263597 hasConceptScore W4387263597C95444343 @default.
- W4387263597 hasLocation W43872635971 @default.
- W4387263597 hasOpenAccess W4387263597 @default.
- W4387263597 hasPrimaryLocation W43872635971 @default.
- W4387263597 hasRelatedWork W2068614944 @default.
- W4387263597 hasRelatedWork W2097331814 @default.
- W4387263597 hasRelatedWork W2905103755 @default.
- W4387263597 hasRelatedWork W2950398730 @default.
- W4387263597 hasRelatedWork W2953763000 @default.
- W4387263597 hasRelatedWork W2999013640 @default.
- W4387263597 hasRelatedWork W3162489004 @default.
- W4387263597 hasRelatedWork W4308681997 @default.
- W4387263597 hasRelatedWork W4361823143 @default.
- W4387263597 hasRelatedWork W4361825482 @default.
- W4387263597 isParatext "false" @default.
- W4387263597 isRetracted "false" @default.
- W4387263597 workType "article" @default.