Tumor suppression through the interaction between CNTN4 and PTPRG attenuates EGFR signaling in colorectal cancer

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Abstract

Abstract Chromosome 3 harbors numerous tumor suppressor genes (TSGs) linked to cancer development and progression. We conducted fine deletion mapping on 179 colorectal cancer (CRC) tumors, and herewith revealed a 3.1 Mb minimal deletion region (MDR) at 3p26.1–p26.3 affecting 31.6% of cases. Allelic loss of the MDR is associated with younger age, distant metastasis, and poorer overall survival. Contactin-4 (CNTN4) is located within the MDR, and its expression was downregulated in 11 of 12 CRC cell lines and 42.3% of colorectal carcinomas. The finding was further verified via the datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases. Ectopic expression of CNTN4 inhibited CRC cell proliferation and anchorage-dependent/independent growth, and promoted apoptosis in vitro. In the xenograft tumor model, CNTN4 suppressed tumor growth through down-regulation of uPA-mediated angiogenesis. Mechanistically, CNTN4 inhibits the EGFR/ERK/c-MYC signaling pathway by directly interacting with PTPRG. CNTN4, a functional tumor suppressor, exhibits early dysregulation, suggesting its potential as a novel prognostic biomarker for CRC initiation and progression.
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Tumor suppression through the interaction between CNTN4 and PTPRG attenuates EGFR signaling in colorectal cancer | 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 Article Tumor suppression through the interaction between CNTN4 and PTPRG attenuates EGFR signaling in colorectal cancer Ya-Chien Yang, Tzu-Ming Jao, Shih-Ci Ciou, Woei-Horng Fang, Shao-Yu Chiang, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6866028/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Chromosome 3 harbors numerous tumor suppressor genes (TSGs) linked to cancer development and progression. We conducted fine deletion mapping on 179 colorectal cancer (CRC) tumors, and herewith revealed a 3.1 Mb minimal deletion region (MDR) at 3p26.1–p26.3 affecting 31.6% of cases. Allelic loss of the MDR is associated with younger age, distant metastasis, and poorer overall survival. Contactin-4 (CNTN4) is located within the MDR, and its expression was downregulated in 11 of 12 CRC cell lines and 42.3% of colorectal carcinomas. The finding was further verified via the datasets from The Cancer Genome Atlas and Gene Expression Omnibus databases. Ectopic expression of CNTN4 inhibited CRC cell proliferation and anchorage-dependent/independent growth, and promoted apoptosis in vitro. In the xenograft tumor model, CNTN4 suppressed tumor growth through down-regulation of uPA-mediated angiogenesis. Mechanistically, CNTN4 inhibits the EGFR/ERK/c-MYC signaling pathway by directly interacting with PTPRG. CNTN4, a functional tumor suppressor, exhibits early dysregulation, suggesting its potential as a novel prognostic biomarker for CRC initiation and progression. Biological sciences/Cancer/Tumour-suppressor proteins Biological sciences/Cancer/Cancer models Biological sciences/Cancer/Tumour biomarkers Full Text Additional Declarations There is no duality of interest Table 1 is available in the Supplementary Files section. Supplementary Files Table1.pdf Table 1 SupplementaryTable1.pdf Supplementary Table 1 SupplementaryTable2.pdf Supplementary Table 2 SupplementaryTable3.pdf Supplementary Table 3 SupplementaryTable4.pdf Supplementary Table 4 Supplementaryinformation.pdf Supplementary information UncroppedwesternblotCNTN4.pdf Uncropped western blot Cite Share Download PDF Status: Under Review 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. 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