[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-383881-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-383881-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","collagen-vi-sustains-cell-stemness-and-chemotherapy-resistance-in-glioblastoma","Collagen VI sustains cell stemness and chemotherapy resistance in glioblastoma","","Microenvironmental factors regulate the phenotype and aggressiveness of glioblastoma (GBM), a lethal brain tumor marked by rapid progression and strong treatment resistance. The extracellular matrix (ECM) shapes cancer cell behavior, stem cell niches, invasiveness, chemotherapy response, survival signaling, and inflammatory recruitment. Findings show collagen VI (COL6) is distributed within the GBM mass and correlates with aggressive, phenotypically immature cells, sustaining stem-like properties and an aggressive transcriptional program. A COL6 co-regulated gene subset supports responses to replicative stress and DNA damage via the ATM/ATR axis, indicating COL6 as a key driver of GBM treatment resistance.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/collagen-vi-sustains-cell-stemness-and-chemotherapy-resistance-in-glioblastoma/383881/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/collagen-vi-sustains-cell-stemness-and-chemotherapy-resistance-in-glioblastoma/383881.png","ImageObject",300,407,{"name":42,"@type":43},"Riley West","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What role does the extracellular matrix play in glioblastoma development and treatment response?","Question",{"text":63,"@type":64},"The ECM regulates cancer cell phenotype and aggressiveness, shapes stem cell niches, influences invasion, and modulates response to chemotherapy. It also supports survival signaling and recruitment of inflammatory cells.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does collagen VI (COL6) relate to GBM cell stemness and chemotherapy resistance?",{"text":68,"@type":64},"COL6 sustains stem-like properties and supports an aggressive transcriptional program that promotes proliferation and survival. It is linked to enhanced responses that help cancer cells resist chemotherapy.",{"name":70,"@type":61,"acceptedAnswer":71},"Which pathway is implicated in COL6-driven resistance mechanisms?",{"text":72,"@type":64},"The abstract identifies the ATM/ATR axis as central to the COL6-mediated response to replicative stress and DNA damage.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},383881,1790309349,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":108},1099523885074,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Cellular and Molecular Life Sciences (2023) 80:233  \n[https://doi.org/10.1007/s00018-023-04887-5](https://doi.org/10.1007/s00018-023-04887-5) Cellular and Molecular Life Sciences  \nCollagen VI sustains cell stemness and chemotherapy resistance in glioblastoma  \nMatilde Cescon1 · Elena Rampazzo2,3 · Silvia Bresolin2,3 · Francesco Da Ros1 · Lorenzo Manfreda2,3 · Alice Cani2,3 · Alessandro Della Puppa4 · Paola Braghetta1 · Paolo Bonaldo1 · Luca Persano2,3  \nReceived: 4 June 2023 / Revised: 11 July 2023 / Accepted: 18 July 2023 / Published online: 28 July 2023 © The Author(s) 2023  \nAbstract  \nMicroenvironmental factors are known fundamental regulators ofthe phenotype and aggressiveness of glioblastoma (GBM), the most lethal brain tumor, characterized by fast progression and marked resistance to treatments. In this context, the extracellular matrix (ECM) is known to heavily influence the behavior of cancer cells from several origins, contributing to stem cell niches, influencing tumor invasiveness and response to chemotherapy, mediating survival signaling cascades, and modulating inflammatory cell recruitment. Here, we show that collagen VI (COL6), an ECM protein widely expressed in both normal and pathological tissues, has a distinctive distribution within the GBM mass, strongly correlated with the most aggressive and phenotypically immature cells. Our data demonstrate that COL6 sustains the stem-like properties of GBM cells and supports the maintenance of an aggressive transcriptional program promoting cancer cell proliferation and survival. In particular, we identified a specific subset of COL6-transcriptionally co-regulated genes, required for the response of cells to replicative stress and DNA damage, supporting the concept that COL6 is an essential stimulus for the activation of GBM cell response and resistance to chemotherapy, through the ATM/ATR axis. Altogether, these findings indicate that COL6 plays a pivotal role in GBM tumor biology, exerting a pleiotropic action across different GBM hallmarks, including phenotypic identity and gene transcription, as well as response to treatments, thus providing valuable information for the understanding of the complex microenvironmental cues underlying GBM malignancy.  \nKeywords Glioblastoma · Extracellular matrix · Collagen VI · Cancer stem cells · Therapy resistance · DNA repair  \n\n| Matilde Cescon and Elena Rampazzo are co-first authors. |\n| --- |\n| Paolo Bonaldo and Luca Persano are co-last authors. |\n\n* Luca Persano [luca.persano@unipd.it](luca.persano@unipd.it)  \n1 Department of Molecular Medicine, University of Padova, Via Ugo Bassi 58/B, 35131 Padua, Italy  \n2 Department of Women and Children’s Health, University of Padova, Via Giustiniani 3, 35127 Padua, Italy  \n3 Istituto di Ricerca Pediatrica-Città della Speranza, Corso Stati Uniti 4, 35128 Padua, Italy  \n4 Department of Neuroscience, Psychology, Pharmacology and Child Health, Neurosurgery Clinic, Academic Neurosurgery, Careggi University Hospital and University of Florence, Largo Palagi 1, 50139 Florence, Italy  \nIntroduction  \nGlioblastoma multiforme (GBM) is the most common malignant brain tumor, and one of the most devastating human cancers, showing resistance to multimodal treatments. GBM patients display a median survival of 16–18 months after diagnosis and a 3-year survival rate of less than 15%[1, 2] . GBM contains a subset of cancer stem cells, known as glioma stem cells (GSCs), which are considered responsible for therapy resistance and tumor relapse [3, 4] . We previously reported the fundamental role played by the GBM hypoxic microenvironment in sustaining a GSC phenotype and driving a concomitant intrinsic resistance to chemotherapy [5] . In particular, we demonstrated that GBM cells distribute along a core-to-periphery gradient within the tumor mass, in parallel with variations in phenotype, proliferation, tumorigenic potential, and response to treatments, depending on hypoxia and, in particular, on HIF-1α a","cbCaioCjqpqRiryy","https://ap.wps.com/l/cbCaioCjqpqRiryy","pdf",2524793,16,"English","# Abstract\n## Introduction\n## Microenvironment and ECM roles\n## Structure and function of collagen VI\n## COL6 expression in glioblastoma and unresolved mechanisms","[{\"question\":\"What role does the extracellular matrix play in glioblastoma development and treatment response?\",\"answer\":\"The ECM regulates cancer cell phenotype and aggressiveness, shapes stem cell niches, influences invasion, and modulates response to chemotherapy. It also supports survival signaling and recruitment of inflammatory cells.\"},{\"question\":\"How does collagen VI (COL6) relate to GBM cell stemness and chemotherapy resistance?\",\"answer\":\"COL6 sustains stem-like properties and supports an aggressive transcriptional program that promotes proliferation and survival. It is linked to enhanced responses that help cancer cells resist chemotherapy.\"},{\"question\":\"Which pathway is implicated in COL6-driven resistance mechanisms?\",\"answer\":\"The abstract identifies the ATM/ATR axis as central to the COL6-mediated response to replicative stress and DNA damage.\"}]","Collagen VI sustains cell stemness and chemotherapy resistance in glioblastoma | PDF",1790260027]