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ASIC3, an extracellular proton sensor, is acid-sensitive, but its function in colorectal cancer acidic tumor microenvironments is not reported. Functional analyses show lactate concentrations accelerate invasion and metastasis, with ASIC3 as a key mediator. De novo lipid synthesis regulates ASIC3 via ACC1 and SCD1, elevating unsaturated fatty acids to induce EMT and promote metastasis.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/asic3-activated-key-enzymes-of-de-novo-lipid-synthesis-supports-lactate-driven-emt-and-the-metastasis-of-colorectal-cancer-cells/331094/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/asic3-activated-key-enzymes-of-de-novo-lipid-synthesis-supports-lactate-driven-emt-and-the-metastasis-of-colorectal-cancer-cells/331094.png","ImageObject",300,407,{"name":92,"@type":93},"Oliver","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is ASIC3’s proposed role in colorectal cancer acidic tumor microenvironments?","Question",{"text":112,"@type":113},"ASIC3 acts as a key mediator in acidic conditions, linking extracellular protons to downstream signaling that supports lactate-driven invasion, EMT, and metastasis in colorectal cancer cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does lactate influence colorectal cancer cell behavior in this study?",{"text":117,"@type":113},"Specific concentrations of lactate accelerate invasion and metastasis, and they cause decreased and desensitized ASIC3 over the stimulation period.",{"name":119,"@type":110,"acceptedAnswer":120},"What pathway connects ASIC3 to EMT and metastasis?",{"text":121,"@type":113},"De novo lipid synthesis regulates ASIC3: down-regulated ASIC3 increases and interacts with ACC1 and SCD1, raising unsaturated fatty acids that induce EMT to promote metastasis.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331094,1790013018,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},8796095461610,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Wan etal. Cell Communication and Signaling (2024) 22:388  \n[https://doi.org/10.1186/s12964-024-01762-z](https://doi.org/10.1186/s12964-024-01762-z)  \nCell Communication and Signaling  \nRESEARCH Open Access  \nASIC3-activated key enzymes of de novo lipid  synthesis supports lactate-driven EMT and the metastasis of colorectal cancer cells  \nXing Wan 1,2, Feng Li 1, Zhigui Li3 and Liming Zhou 1*  \nAbstract  \nAcidic microenvironments is a cancer progression driver, unclear core mechanism hinders the discovery of new diagnostic or therapeutic targets. ASIC3 is an extracellular proton sensor and acid-sensitive, but its role in acidic tumor microenvironment of colorectal cancer is not reported. Functional analysis data show that colorectal cancer cells respond to specific concentration of lactate to accelerate invasion and metastasis, and ASIC3 is the main actor in this process. Mechanism reveal de novo lipid synthesis is a regulatory process of ASIC3, down-regulated ASIC3 increases and interacts with ACC1 and SCD1, which are key enzymes in de novo lipid synthesis pathway, this interaction results in increased unsaturated fatty acids, which in turn induce EMT to promote metastasis, andoverexpression of ASIC3 reduces acidic TME-enhanced colorectal cancer metastasis. Clinical samples of colorectal cancer also exhibit decreased ASIC3 expression, and low ASIC3 expression is associated with metastasis and stage of colorectal cancer. This study is the first to identify the role of the ASIC3-ACC1/SCD1 axis in acid-enhanced colorectal cancer metastasis. The expression pattern of ASIC3 in colorectal cancer differs significantly from that in other types of cancers, ASIC3 may serve as a novel and reliable marker for acidic microenvironmental in colorectal cancer, and potentially a therapeutic target.  \nKeywords Colorectal cancer, Acidic tumor microenvironment, ASIC3, De novo lipid synthesis, EMT, Metastasis  \nBackground  \nCancer is a complex and polymorphic disease, with its surrounding environment being a key factor that sets it apart from normal tissues and influences cancer progression and behavior. This environment, known as the tumor microenvironment (TME), is characterized by various features. While hypoxia is extensively studied [1], acidity is another prevalent yet less explored characteristic. Tumor tissues often exhibit a pH of 6.6 or lower [2].  \n*Correspondence: Liming Zhou [zhoulim@scu.edu.cn](zhoulim@scu.edu.cn)  \nFull list of author information is available at the end of the article  \nAlthough not as extensively studied as hypoxia, an increasing number of studies have focused on the effect of acidic TME on tumor phenotypes. Recent research indicates that the acidic TME significantly influences carcinogenesis by modulating various aspects of cancer behavior [3], such as proliferation [4], invasion [5], metastasis [6], stemness, and cell death [7]. Nevertheless, the clinical efficacy of acidosis-targeted treatments varies depending on the cancer type, pathological stage and metastatic phase. A mere 0.1 unit change in the intracellular and extracellular pH ratio can trigger biological or pathological effects [8]. These findings suggest that acidity-mediated tumor response are organ-or cancer-specific.  \n© The Author(s) 2024, corrected publication 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercialNoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the mater","cbCaidRJljP1xJW7","https://ap.wps.com/l/cbCaidRJljP1xJW7","pdf",18952779,17,"English","# Abstract\n# Background\n## Tumor microenvironment acidity and its impact","[{\"question\":\"What is ASIC3’s proposed role in colorectal cancer acidic tumor microenvironments?\",\"answer\":\"ASIC3 acts as a key mediator in acidic conditions, linking extracellular protons to downstream signaling that supports lactate-driven invasion, EMT, and metastasis in colorectal cancer cells.\"},{\"question\":\"How does lactate influence colorectal cancer cell behavior in this study?\",\"answer\":\"Specific concentrations of lactate accelerate invasion and metastasis, and they cause decreased and desensitized ASIC3 over the stimulation period.\"},{\"question\":\"What pathway connects ASIC3 to EMT and metastasis?\",\"answer\":\"De novo lipid synthesis regulates ASIC3: down-regulated ASIC3 increases and interacts with ACC1 and SCD1, raising unsaturated fatty acids that induce EMT to promote metastasis.\"}]","ASIC3-activated key enzymes of de novo lipid synthesis supports lactate-driven EMT and the metastasis of colorectal cancer cells | PDF",1789991777,43]