Repository logo
 
Publication

Therapy-induced cellular senescence induces epithelial-to-mesenchymal transition and increases invasiveness in rectal cancer

2016Journal article Restricted access
Simple item page
dc.contributor.authorTato-Costa, Joana
dc.contributor.authorCasimiro, Sandra
dc.contributor.authorPacheco, Teresa
dc.contributor.authorPires, Ricardo
dc.contributor.authorFernandes, Afonso
dc.contributor.authorAlho, Irina
dc.contributor.authorPereira, Pedro
dc.contributor.authorCosta, Paulo M.
dc.contributor.authorCastelo, Henrique Bicha
dc.contributor.authorFerreira, João
dc.contributor.authorCosta, Luis
dc.date.accessioned2022-09-23T15:49:21Z
dc.date.available2022-09-23T15:49:21Z
dc.date.issued2016
dc.description© 2015 Elsevier Inc. All rights reserved.pt_PT
dc.description.abstractIntroduction: DNA damaging agents and ionizing radiation used in the therapy of human cancers can induce senescence of cancer cells. Senescent cells exhibit a secretory phenotype (senescence-associated secretome [SAS]) that can affect cancer cell behavior and, eventually, clinical prognosis. We assessed the effects of the SAS on the induction of epithelial-to-mesenchymal transition (EMT) in vitro and in clinical samples from patients with rectal cancer who had undergone neoadjuvant chemoradiotherapy (CRT). Materials and methods: Colorectal cancer cells (HCT 116) were induced into senescence by exposure to either 5-fluorouracil (5-FU) or doxorubicin. The senescent state was confirmed by staining for senescence-associated β-galactosidase (SA-β-Gal). The paracrine effects of SASs were assessed on proliferating HCT 116 cells. The quantified parameters were cell proliferation, invasive capacity, and induction of EMT. Senescence and EMT in clinical samples were assessed by the expression levels (reverse transcriptase-quantitative polymerase chain reaction) of genes related to senescence and EMT after laser-assisted microdissection of cancer cell clusters that stained either positive or negative for SA-β-Gal. Results: We have shown that cultured colon cancer cells induced into senescence by exposure to 5-FU exhibit a SAS capable of paracrine induction of EMT in colon and rectal cancer cell lines and increased cell invasion in vitro. Using laser-assisted microdissection, we found that in rectal cancer samples from patients treated with neoadjuvant CRT, tumor cell niches enriched for senescent cells bookmark regions of increased mRNA expression levels of EMT-related proteins (Slug, Snail, vimentin) compared with the nearby senescent-null tumor cell niches. Conclusion: We have provided, first-hand, strongly suggestive evidence that senescent cancer cells emerging in the context of neoadjuvant CRT for rectal cancer influenced the tumor microenvironment by promoting EMT by way of short-range interactions.pt_PT
dc.description.sponsorshipThis work was supported by the Histology and Comparative Pathology Laboratory and the Bioimaging Unit of the Instituto de Medicina Molecular for technical support. J. Tato-Costa, S. Casimiro, I. Alho, and P. Pereira were supported by fellowships from Fundação para a Ciência e Tecnologia (grants SFRH/BD/45219/2008, SFRH/BPD/34801/2007, SFRH/BD/44716/2008, and SFRH/BD/45502/2008, respectively). João Ferreira receives support from Gulbenkiam Foundation (grant 96526/2009).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationClin Colorectal Cancer. 2016 Jun;15(2):170-178.e3pt_PT
dc.identifier.doi10.1016/j.clcc.2015.09.003pt_PT
dc.identifier.eissn1938-0674
dc.identifier.issn1533-0028
dc.identifier.urihttp://hdl.handle.net/10451/54576
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationSTROMAL-EPITHELIAL INTERACTIONS IN RECTAL CANCER:ROLE OF CHEMORADIOTHERAPY - INDUCED SENESCENCE IN CLINICAL OUTCOME
dc.relationMECHANISMS OF INVASION AND PROGRESSION OF CANCER IN BONE: ROLE OF MATRIX METALLOPROTEASES
dc.relationTHE IMPORTANCE OF LMW-PTP LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE ON THE PROGRESSION OF BONE METASTASIS AND THERAPEUTIC RESPONSE
dc.relationCELLULAR SENESCENCE IN THE CONTEXT OF ANTI-CANCER CHEMOTHERAPY
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/clinical-colorectal-cancerpt_PT
dc.subject5-Fluorouracilpt_PT
dc.subjectNeoadjuvant chemotherapypt_PT
dc.subjectRectal cancerpt_PT
dc.subjectSenescence-associated secretory phenotypept_PT
dc.subjectTherapy-induced senescencept_PT
dc.titleTherapy-induced cellular senescence induces epithelial-to-mesenchymal transition and increases invasiveness in rectal cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleSTROMAL-EPITHELIAL INTERACTIONS IN RECTAL CANCER:ROLE OF CHEMORADIOTHERAPY - INDUCED SENESCENCE IN CLINICAL OUTCOME
oaire.awardTitleMECHANISMS OF INVASION AND PROGRESSION OF CANCER IN BONE: ROLE OF MATRIX METALLOPROTEASES
oaire.awardTitleTHE IMPORTANCE OF LMW-PTP LOW MOLECULAR WEIGHT PROTEIN TYROSINE PHOSPHATASE ON THE PROGRESSION OF BONE METASTASIS AND THERAPEUTIC RESPONSE
oaire.awardTitleCELLULAR SENESCENCE IN THE CONTEXT OF ANTI-CANCER CHEMOTHERAPY
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F45219%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/PIDDAC/SFRH%2FBPD%2F34801%2F2007/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F44716%2F2008/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/FARH/SFRH%2FBD%2F45502%2F2008/PT
oaire.citation.endPage178.e3pt_PT
oaire.citation.issue2pt_PT
oaire.citation.startPage170pt_PT
oaire.citation.titleClinical Colorectal Cancerpt_PT
oaire.citation.volume15pt_PT
oaire.fundingStreamPIDDAC
oaire.fundingStreamFARH
person.familyNameCara de Anjo Casimiro
person.familyNamePacheco
person.familyNameDuarte
person.familyNameCosta
person.familyNameCastelo
person.familyNameFerreira
person.familyNameCosta
person.givenNameSandra Cristina
person.givenNameTeresa
person.givenNameIrina
person.givenNamePaulo Matos
person.givenNameHenrique Bicha
person.givenNameJoão
person.givenNameLuis
person.identifier.ciencia-id0F12-5181-0B22
person.identifier.ciencia-id651D-2E22-AB73
person.identifier.ciencia-id0415-4404-DDBE
person.identifier.ciencia-id041E-4ADE-FB64
person.identifier.orcid0000-0002-6917-4477
person.identifier.orcid0000-0002-5506-0233
person.identifier.orcid0000-0002-3190-7479
person.identifier.orcid0000-0002-7550-8285
person.identifier.orcid0000-0002-8299-922X
person.identifier.orcid0000-0002-8044-8926
person.identifier.orcid0000-0002-4782-7318
person.identifier.ridABD-1573-2021
person.identifier.scopus-author-id14043403400
person.identifier.scopus-author-id55977165500
person.identifier.scopus-author-id6505817424
person.identifier.scopus-author-id55910601500
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationfd665de1-a7e6-4638-94c3-ecc645f84607
relation.isAuthorOfPublication45c53fd3-4da2-4d58-8c15-b13968b8689d
relation.isAuthorOfPublicationac30657e-6e0f-4437-8aea-bb1bcf05e1c5
relation.isAuthorOfPublication7f62714b-b0f1-4d22-a3a5-de04bc736cca
relation.isAuthorOfPublicatione4f3ede3-b6ba-4c7b-bd3d-42e49f36c6d1
relation.isAuthorOfPublication08990620-f70a-4411-a2b5-580054cb76b1
relation.isAuthorOfPublication8a2ab4c6-ba86-4433-b4b7-6256d81890e5
relation.isAuthorOfPublication.latestForDiscovery45c53fd3-4da2-4d58-8c15-b13968b8689d
relation.isProjectOfPublication354306ca-1304-4825-93d9-f33c451ffaac
relation.isProjectOfPublicationf9b339ad-1b8e-4016-8000-10323ac83d5b
relation.isProjectOfPublicationa1926b29-e538-4f0d-b8f7-ae768fae7f22
relation.isProjectOfPublicationbb9b9d76-eda4-4b02-84b1-bdf471227832
relation.isProjectOfPublication.latestForDiscoveryf9b339ad-1b8e-4016-8000-10323ac83d5b

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Therapy_cellular.pdf
Size:
2.33 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.2 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

IMM - Artigos em Revistas Internacionais
FM - Artigos em Revistas Internacionais