Calix[6]arene diminishes receptor tyrosine kinase lifespan in pancreatic cancer cells and inhibits their migration and invasion efficiency

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dc.creatorKarin Juliane Pelizzaro Rocha-Brito
dc.creatorEmanuella Maria Barreto Fonseca
dc.creatorBreno Germano de Freitas Oliveira
dc.creatorÂngelo de Fátima
dc.creatorCarmen Veríssima Ferreira-Halder
dc.date.accessioned2024-10-29T22:45:49Z
dc.date.accessioned2025-09-08T23:17:17Z
dc.date.available2024-10-29T22:45:49Z
dc.date.issued2020
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipFAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo
dc.identifier.doihttps://doi.org/10.1016/j.bioorg.2020.103881
dc.identifier.issn0045-2068
dc.identifier.urihttps://hdl.handle.net/1843/77711
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofBioorganic Chemistry
dc.rightsAcesso Restrito
dc.subjectCalixarenos
dc.subjectCancer -Tratamento
dc.subjectMetástase
dc.subjectCélulas cancerosas - Proliferação
dc.subject.otherCalix[6]arene
dc.subject.otherPancreatic cancer
dc.subject.otherReceptor tyrosine kinases
dc.subject.otherEndocytosis
dc.subject.otherMigration
dc.titleCalix[6]arene diminishes receptor tyrosine kinase lifespan in pancreatic cancer cells and inhibits their migration and invasion efficiency
dc.typeArtigo de periódico
local.citation.spage103881
local.citation.volume100
local.description.resumoPancreatic cancer is a challenging malignancy, mainly due to aggressive regional involvement, early systemic dissemination, high recurrence rate, and subsequent low patient survival. Scientific advances have contributed in particular by identification of molecular targets as well as the definition of the mechanism of action of the drug candidate in the cellular microenvironment. Previously, we have reported the identification of the molecular mechanisms by which calix[6]arene (CLX6) reduces the viability and proliferation of pancreatic cancer cells. Now, we show the biochemical mechanisms by which CLX6 decreases the aggressiveness of Panc-1 cells, focusing specifically on receptor tyrosine kinases (RTK). The results show that clathrin-mediated endocytosis is involved in CLX6-induced AXL receptor tyrosine kinase degradation in Panc-1 cells. This response may be related to the interaction of CLX6 with the tyrosine kinase receptor binding site (such as AXL). As a result, RTK is internalized and degraded by endocytosis, a condition that negatively impacts events dependent on its signaling. Additionally, CLX6 inhibits migration and invasion of Panc-1 cells by downregulating FAK (downstream mediator of AXL) activity and reducing expression levels of MMP2 and MMP9, directly related to the metastatic profile of these cells. It is noteworthy that according to the mechanism proposed here, CLX6 appears as a candidate to be used in therapeutic protocols of patients that display high expression of AXL and consequently, poor diagnosis.
local.identifier.orcidhttps://orcid.org/0000-0003-4499-314X
local.identifier.orcidhttps://orcid.org/0000-0003-2344-5590
local.publisher.countryBrasil
local.publisher.departmentICX - DEPARTAMENTO DE QUÍMICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S0045206820303138

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