Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance

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dc.contributor.author Pietilä, Elina A.
dc.contributor.author Gonzalez-Molina, Jordi
dc.contributor.author Moyano-Galceran, Lidia
dc.contributor.author Jamalzadeh, Sanaz
dc.contributor.author Zhang, Kaiyang
dc.contributor.author Lehtinen, Laura
dc.contributor.author Turunen, S. Pauliina
dc.contributor.author Martins, Tomas A.
dc.contributor.author Gultekin, Okan
dc.contributor.author Lamminen, Tarja
dc.contributor.author Kaipio, Katja
dc.contributor.author Joneborg, Ulrika
dc.contributor.author Hynninen, Johanna
dc.contributor.author Hietanen, Sakari
dc.contributor.author Grenman, Seija
dc.contributor.author Lehtonen, Rainer
dc.contributor.author Hautaniemi, Sampsa
dc.contributor.author Carpen, Olli
dc.contributor.author Carlson, Joseph W.
dc.contributor.author Lehti, Kaisa
dc.date.accessioned 2021-09-20T08:48:02Z
dc.date.available 2021-09-20T08:48:02Z
dc.date.issued 2021-06-23
dc.identifier.citation Pietilä , E A , Gonzalez-Molina , J , Moyano-Galceran , L , Jamalzadeh , S , Zhang , K , Lehtinen , L , Turunen , S P , Martins , T A , Gultekin , O , Lamminen , T , Kaipio , K , Joneborg , U , Hynninen , J , Hietanen , S , Grenman , S , Lehtonen , R , Hautaniemi , S , Carpen , O , Carlson , J W & Lehti , K 2021 , ' Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance ' , Nature Communications , vol. 12 , no. 1 , 3904 . https://doi.org/10.1038/s41467-021-24009-8
dc.identifier.other PURE: 168609509
dc.identifier.other PURE UUID: 014f7611-daf8-4b30-b75c-e6f5431f2169
dc.identifier.other WOS: 000668769000003
dc.identifier.other ORCID: /0000-0002-7749-2694/work/100256751
dc.identifier.other ORCID: /0000-0002-8343-0318/work/100257315
dc.identifier.other ORCID: /0000-0003-0209-9369/work/100258846
dc.identifier.uri http://hdl.handle.net/10138/334455
dc.description.abstract Due to its dynamic nature, the evolution of cancer cell-extracellular matrix (ECM) crosstalk, critically affecting metastasis and treatment resistance, remains elusive. Our results show that platinum-chemotherapy itself enhances resistance by progressively changing the cancer cell-intrinsic adhesion signaling and cell-surrounding ECM. Examining ovarian high-grade serous carcinoma (HGSC) transcriptome and histology, we describe the fibrotic ECM heterogeneity at primary tumors and distinct metastatic sites, prior and after chemotherapy. Using cell models from systematic ECM screen to collagen-based 2D and 3D cultures, we demonstrate that both specific ECM substrates and stiffness increase resistance to platinum-mediated, apoptosis-inducing DNA damage via FAK and beta 1 integrin-pMLC-YAP signaling. Among such substrates around metastatic HGSCs, COL6 was upregulated by chemotherapy and enhanced the resistance of relapse, but not treatment-naive, HGSC organoids. These results identify matrix adhesion as an adaptive response, driving HGSC aggressiveness via co-evolving ECM composition and sensing, suggesting stromal and tumor strategies for ECM pathway targeting. Platinum chemotherapy is standard of care in ovarian cancers but treatment resistance commonly develops. Here, the authors show that the extracellular microenvironment is modulated following chemotherapy and the changes in matrix proteins and stiffness alter the cell death response of tumour cells. en
dc.format.extent 19
dc.language.iso eng
dc.relation.ispartof Nature Communications
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject EXTRACELLULAR-MATRIX
dc.subject COLLAGEN-VI
dc.subject METASTASIS
dc.subject RESISTANCE
dc.subject APOPTOSIS
dc.subject INVASION
dc.subject STROMA
dc.subject ACTIN
dc.subject CELLS
dc.subject 3122 Cancers
dc.subject 3123 Gynaecology and paediatrics
dc.title Co-evolution of matrisome and adaptive adhesion dynamics drives ovarian cancer chemoresistance en
dc.type Article
dc.contributor.organization Research Program in Systems Oncology
dc.contributor.organization Kaisa Irene Lehti / Principal Investigator
dc.contributor.organization INDIVIDRUG - Individualized Drug Therapy
dc.contributor.organization Sampsa Hautaniemi / Principal Investigator
dc.contributor.organization Research Programs Unit
dc.contributor.organization HUSLAB
dc.contributor.organization Biosciences
dc.contributor.organization Faculty Common Matters
dc.contributor.organization Bioinformatics
dc.contributor.organization Department of Biochemistry and Developmental Biology
dc.contributor.organization Precision Cancer Pathology
dc.contributor.organization Department of Pathology
dc.contributor.organization Olli Mikael Carpen / Principal Investigator
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1038/s41467-021-24009-8
dc.relation.issn 2041-1723
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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