Impact of SLC16A8 on Tumor Microenvironment and Angiogenesis in Colorectal Cancer: New Therapeutic Target Insights

Impact of SLC16A8 on Tumor Microenvironment and Angiogenesis in Colorectal Cancer: New Therapeutic Target Insights | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of SLC16A8 on Tumor Microenvironment and Angiogenesis in Colorectal Cancer: New Therapeutic Target Insights Hongpeng Tian, Zhongxiang Xiao, Bowen Su, Yixuan Li, Hong Peng, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4526158/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aim SLC16A8, a lactate efflux transporter, is upregulated in various cancers, but its effect on tumor microenvironments remains understudied. This research explores its role in colorectal cancer and the impact on the associated microenvironment consisting of vascular endothelial cells. Methods Hypoxic conditions prompted examination of SLC16A8 expression, glycolysis, lactate efflux, and Warburg effect correlations in colorectal cancer cell lines. Co-culture with HUVEC allowed for EndMT characterization, revealing lactate efflux's influence. Knockdown of SLC16A8 in colorectal cancer cells enabled relevant phenotype tests and tumorigenesis experiments, investigating tumor growth, blood vessel distribution, and signaling pathway alterations. Results Under hypoxic conditions, SLC16A8 upregulation not only promoted anaerobic glycolysis, LDHA, and PKM2 expression in colorectal cancer cells but also suggested Warburg effect involvement. Co-culturing with HUVEC triggered an increase in EndMT characteristics in endothelial cells. Knocking down SLC16A8 reversed these phenotypes in both cell types. In vivo , SLC16A8 inhibition led to reduced tumor growth, decreased angiogenesis, and enhanced apoptosis signals. SLC16A8 plays a pivotal role in promoting tumor angiogenesis and fostering a favorable environment for colorectal cancer development. Conclusions The findings emphasize the importance of addressing lactate efflux in cancer therapy and warrant further investigation into SLC16A8 as a potential therapeutic target. SLC16A8 colorectal cancer hypoxia glycolysis angiogenesis Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4526158","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":314500926,"identity":"e8b477e6-77fe-4d60-90e9-2a980ab7e74a","order_by":0,"name":"Hongpeng Tian","email":"","orcid":"","institution":"The Affiliated Hospital of North Sichuan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Hongpeng","middleName":"","lastName":"Tian","suffix":""},{"id":314500927,"identity":"146dd3ba-9d16-4e6b-a92e-0e0258960361","order_by":1,"name":"Zhongxiang Xiao","email":"","orcid":"","institution":"The Affiliated Hospital of North 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angiogenesis","lastPublishedDoi":"10.21203/rs.3.rs-4526158/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4526158/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eAim\u003c/h2\u003e \u003cp\u003eSLC16A8, a lactate efflux transporter, is upregulated in various cancers, but its effect on tumor microenvironments remains understudied. This research explores its role in colorectal cancer and the impact on the associated microenvironment consisting of vascular endothelial cells.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eHypoxic conditions prompted examination of SLC16A8 expression, glycolysis, lactate efflux, and Warburg effect correlations in colorectal cancer cell lines. Co-culture with HUVEC allowed for EndMT characterization, revealing lactate efflux's influence. Knockdown of SLC16A8 in colorectal cancer cells enabled relevant phenotype tests and tumorigenesis experiments, investigating tumor growth, blood vessel distribution, and signaling pathway alterations.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eUnder hypoxic conditions, SLC16A8 upregulation not only promoted anaerobic glycolysis, LDHA, and PKM2 expression in colorectal cancer cells but also suggested Warburg effect involvement. Co-culturing with HUVEC triggered an increase in EndMT characteristics in endothelial cells. Knocking down SLC16A8 reversed these phenotypes in both cell types. \u003cem\u003eIn vivo\u003c/em\u003e, SLC16A8 inhibition led to reduced tumor growth, decreased angiogenesis, and enhanced apoptosis signals. SLC16A8 plays a pivotal role in promoting tumor angiogenesis and fostering a favorable environment for colorectal cancer development.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe findings emphasize the importance of addressing lactate efflux in cancer therapy and warrant further investigation into SLC16A8 as a potential therapeutic target.\u003c/p\u003e","manuscriptTitle":"Impact of SLC16A8 on Tumor Microenvironment and Angiogenesis in Colorectal Cancer: New Therapeutic Target Insights","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-19 15:20:36","doi":"10.21203/rs.3.rs-4526158/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eea3218d-367b-4418-b1d4-49a434afa369","owner":[],"postedDate":"June 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-07-31T10:53:42+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-19 15:20:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4526158","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4526158","identity":"rs-4526158","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}