{"doi":"10.3390/ijms231911722","title":"Collagen Type XI Inhibits Lung Cancer-Associated Fibroblast Functions and Restrains the Integrin Binding Site Availability on Collagen Type I Matrix","abstract":"<jats:p>The tumor microenvironment, including cancer-associated fibroblast (CAF), plays an active role in non-small cell lung cancer (NSCLC) development and progression. We previously reported that collagen type XI and integrin α11, a collagen receptor, were upregulated in NSCLC; the latter promotes tumor growth and metastasis. We here explored the role of collagen type XI in NSCLC stroma. We showed that the presence of collagen type XI in collagen type I matrices inhibits CAF-mediated collagen remodeling and cell migration. This resulted in the inhibition of CAF-dependent lung-tumor cell invasion. Among the collagen receptors expressed on CAF, we determined that DDR2 and integrin α2β1, but not integrin α11β1, mediated the high-affinity binding to collagen type XI. We further demonstrated that collagen type XI restrained the integrin binding site availability on collagen type I matrices, thus limiting cell interaction with collagen type I. As a consequence, CAFs failed to activate FAK, p38 and Akt one hour after they interacted with collagen type I/XI. We concluded that collagen type XI may have a competitive negative feedback role on the binding of collagen type I to its receptors.</jats:p>","journal":"International Journal of Molecular Sciences","year":2022,"id":47460,"datarank":0.5051859468201618,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.13244994935196172,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.13244994935196172,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":10,"citers_with_citation_signal":9,"citers_with_endowment":9,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":16386,"name":"Maryam Khalil","orcid":"0009-0002-5397-9841","position":1,"is_corresponding":false},{"id":219679,"name":"Roya Navab","orcid":null,"position":2,"is_corresponding":false},{"id":219680,"name":"Ming-Sound Tsao","orcid":"0000-0002-9160-5405","position":3,"is_corresponding":false},{"id":219678,"name":"Cédric Zeltz","orcid":"0000-0002-7828-6868","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Collagen Type XI Inhibits Lung Cancer-Associated Fibroblast Functions and Restrains the Integrin Binding Site Availability on Collagen Type I Matrix","abstract":"<jats:p>The tumor microenvironment, including cancer-associated fibroblast (CAF), plays an active role in non-small cell lung cancer (NSCLC) development and progression. We previously reported that collagen type XI and integrin α11, a collagen receptor, were upregulated in NSCLC; the latter promotes tumor growth and metastasis. We here explored the role of collagen type XI in NSCLC stroma. We showed that the presence of collagen type XI in collagen type I matrices inhibits CAF-mediated collagen remodeling and cell migration. This resulted in the inhibition of CAF-dependent lung-tumor cell invasion. Among the collagen receptors expressed on CAF, we determined that DDR2 and integrin α2β1, but not integrin α11β1, mediated the high-affinity binding to collagen type XI. We further demonstrated that collagen type XI restrained the integrin binding site availability on collagen type I matrices, thus limiting cell interaction with collagen type I. As a consequence, CAFs failed to activate FAK, p38 and Akt one hour after they interacted with collagen type I/XI. We concluded that collagen type XI may have a competitive negative feedback role on the binding of collagen type I to its receptors.</jats:p>","is_dataset_classified":null,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36233024","pmcid":"PMC9569509","openalex_id":"https://openalex.org/W4303699940","authors":[],"funders":[{"funder_name":"Canadian Institute of Health Research Foundation","grant_id":"FDN-148395","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Ontario Ministry of Health and Long-Term Care","grant_id":"","title":null}],"total_grants":3,"fwci":1.3705,"citation_percentile":0.7889133,"influential_citations":0,"citation_trend":[{"year":2024,"count":3},{"year":2025,"count":7}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/23/19/11722/pdf?version=1664793147","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/23/19/11722/pdf?version=1664793147","host_type":"GOLD"},{"url":"https://www.mdpi.com/1422-0067/23/19/11722/pdf?version=1664793147","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/23/19/11722/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms231911722","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36233024","host_type":"repository"},{"url":"https://doaj.org/article/37ec04d5fe5c40eca1d5d9782440e752","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/ijms231911722","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9569509","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9569509","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9569509?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3390/ijms231911722","host_type":""}],"fields_of_study":["Cell Adhesion Molecules Research","Cellular Mechanics and Interactions","Protease and Inhibitor Mechanisms","Medicine","Biology","0301 basic medicine","03 medical and health sciences","Binding Sites","Cancer-Associated Fibroblasts","Carcinoma, Non-Small-Cell Lung","Collagen","Collagen Type I","Collagen Type XI","Humans","Integrin alpha2beta1","Lung","Lung Neoplasms","Proto-Oncogene Proteins c-akt","Receptors, Collagen","Tumor Microenvironment"],"mesh_terms":["Cancer-Associated Fibroblasts","Binding Sites","Carcinoma, Non-Small-Cell Lung","Collagen","Humans","Lung","Lung Neoplasms","Collagen Type I","Collagen Type XI","Receptors, Collagen","Integrin alpha2beta1","Proto-Oncogene Proteins c-akt","Tumor Microenvironment"],"keywords":["Collagen receptor","Collagen, type I, alpha 1","Integrin","Type I collagen","Chemistry","Fibroblast","Cancer research","Extracellular matrix","Receptor","Cell biology","Biology","Endocrinology","Biochemistry","In vitro","Collagen","Non-small cell lung cancer","Col11a1","Cancer-associated Fibroblast","Binding Sites","Lung Neoplasms","Receptors, Collagen","Collagen Type XI","Article","Collagen Type I","Cancer-Associated Fibroblasts","Carcinoma, Non-Small-Cell Lung","Tumor Microenvironment","Humans","<i>COL11A1</i>","Integrin alpha2beta1","Lung","Proto-Oncogene Proteins c-akt"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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