Sox9 Elevation Acts With Canonical Wnt Signaling To Drive Gastric Cancer Progression

dc.creatorSantos
dc.creatorJuliana Carvalho; Carrasco-Garcia
dc.creatorEstefania; Garcia-Puga
dc.creatorMikel; Aldaz
dc.creatorPaula; Montes
dc.creatorMilagrosa; Fernandez-Reyes
dc.creatorMaria; de Oliveira
dc.creatorCaroline Candida; Lawrie
dc.creatorCharles H.; Arauzo-Bravo
dc.creatorMarcos J.; Ribeiro
dc.creatorMarcelo Lima; Matheu
dc.creatorAnder
dc.date2016
dc.datenov
dc.date2017-11-13T11:31:02Z
dc.date2017-11-13T11:31:02Z
dc.date.accessioned2018-03-29T05:46:06Z
dc.date.available2018-03-29T05:46:06Z
dc.identifierCancer Research. Amer Assoc Cancer Research, v. 76, p. 6735 - 6746, 2016.
dc.identifier0008-5472
dc.identifier1538-7445
dc.identifierWOS:000388742100030
dc.identifier10.1158/0008-5472.CAN-16-1120
dc.identifierhttp://cancerres.aacrjournals.org/content/76/22/6735.short
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/325846
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1362852
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionGastric cancer remains one of the leading causes of global cancer mortality due to therapy resistance, with Helicobacter pylori (H. pylori) infection being a major risk factor. In this study, we report the significance of an elevation of the stem cell regulator SOX9 in bacteria-infected human gastritis and cancer samples, paralleling increased levels of TNF alpha. SOX9 elevation was more intense in specimens containing the pathogenically significant cagA+ strains of H. pylori. Notably, we found that SOX9 was required for bacteria-induced gastric cancer cell proliferation, increased levels of beta-catenin, and acquisition of stem cell-like properties. Analysis of three large clinical cohorts revealed elevated SOX9 levels in gastric cancer with advanced tumor stage and poor patient survival. Functionally, SOX9 silencing in gastric cancer cells enhanced apoptosis and senescence, concomitantly with a blockade to self-renewal and tumor-initiating capability. Paralleling these effects, we also found SOX9 to mediate cisplatin chemoresistance associated with reduced disease-free survival. Mechanistic interactions between SOX9 and b-catenin expression suggested the existence of a regulatory role for SOX9 targeting the WNT canonical pathway. Taken together, our findings establish the significance of SOX9 in gastric cancer pathobiology and heterogeneity, with implications for targeting WNT-SOX9 signaling as a rational therapeutic strategy.
dc.description76
dc.description22
dc.description6735
dc.description6746
dc.descriptionInstituto Carlos III
dc.descriptionFEDER funds [CP10/00539, PI13/02277]
dc.descriptionEuropean Union (Marie Curie CIG) [2012/712404, REFBIO13/BIOD/011]
dc.descriptionBrazilian National Council for Scientific and Technological Development (CNPq) [300975/2014-7]
dc.descriptionSao Paulo Research Foundation [2014/11862-6]
dc.descriptionFAPESP
dc.descriptionUniversity of the Basque Country [15/245]
dc.descriptionSpanish Association Against Cancer (AECC Gipuzkoa)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageEnglish
dc.publisherAmer Assoc Cancer Research
dc.publisherPhiladelphia
dc.relationCancer Research
dc.rightsfechado
dc.sourceWOS
dc.titleSox9 Elevation Acts With Canonical Wnt Signaling To Drive Gastric Cancer Progression
dc.typeArtículos de revistas


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