{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T09:47:32Z","timestamp":1768816052897,"version":"3.49.0"},"reference-count":30,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa Operacional Regional do Norte","award":["NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678"]}]},{"name":"Programa Operacional Regional do Norte","award":["PTDC\/BIA-CEL\/0456\/2021"],"award-info":[{"award-number":["PTDC\/BIA-CEL\/0456\/2021"]}]},{"name":"Programa Operacional Regional do Norte","award":["CEECINST\/00131\/2021"],"award-info":[{"award-number":["CEECINST\/00131\/2021"]}]},{"name":"European Regional Development Fund","award":["NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678"]}]},{"name":"European Regional Development Fund","award":["PTDC\/BIA-CEL\/0456\/2021"],"award-info":[{"award-number":["PTDC\/BIA-CEL\/0456\/2021"]}]},{"name":"European Regional Development Fund","award":["CEECINST\/00131\/2021"],"award-info":[{"award-number":["CEECINST\/00131\/2021"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["PTDC\/BIA-CEL\/0456\/2021"],"award-info":[{"award-number":["PTDC\/BIA-CEL\/0456\/2021"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["CEECINST\/00131\/2021"],"award-info":[{"award-number":["CEECINST\/00131\/2021"]}]},{"name":"FCT","award":["NORTE-01-0145-FEDER-072678"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-072678"]}]},{"name":"FCT","award":["PTDC\/BIA-CEL\/0456\/2021"],"award-info":[{"award-number":["PTDC\/BIA-CEL\/0456\/2021"]}]},{"name":"FCT","award":["CEECINST\/00131\/2021"],"award-info":[{"award-number":["CEECINST\/00131\/2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Gastric cancer is the fifth most common cancer and the fourth cause of global cancer mortality. The identification of new biomarkers and drug targets is crucial to allow the better prognosis and treatment of patients. The mitotic spindle positioning (MISP) protein has the function of correcting mitotic spindle positioning and centrosome clustering and has been implicated in the cytokinesis and migration of cancer cells. The goal of this work was to evaluate the expression and clinical relevance of MISP in gastric cancer. MISP expression was evaluated by immunohistochemistry in a single hospital series (n = 286) of gastric adenocarcinomas and compared with normal gastric mucosa and intestinal metaplasia, a preneoplastic lesion. MISP was detected on the membrane in 83% of the cases, being overexpressed in gastric cancer compared to normal gastric mucosa (n = 10). Its expression was negatively associated with diffuse and poorly cohesive types. On the other hand, it was strongly expressed in intestinal metaplasia where it was associated with MUC2 and CDX2 expression. Furthermore, when we silenced MISP in vitro, a significant decrease in the viability of gastric carcinoma cells was observed. In conclusion, MISP is overexpressed in gastric cancer, being associated with an intestinal phenotype in gastric carcinogenesis and having a role in cellular proliferation.<\/jats:p>","DOI":"10.3390\/curroncol31050210","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T11:26:17Z","timestamp":1715858777000},"page":"2769-2779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["MISP Is Overexpressed in Intestinal Metaplasia and Gastric Cancer"],"prefix":"10.3390","volume":"31","author":[{"given":"Tom\u00e1s","family":"Vilarinho","sequence":"first","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5780-9842","authenticated-orcid":false,"given":"Diana","family":"P\u00e1dua","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2460-6720","authenticated-orcid":false,"given":"Bruno","family":"Pereira","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4766-9831","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Mesquita","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"}]},{"given":"Raquel","family":"Almeida","sequence":"additional","affiliation":[{"name":"i3S\u2014Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal"},{"name":"IPATIMUP\u2014Institute of Molecular Pathology and Immunology, University of Porto, 4200-465 Porto, Portugal"},{"name":"Biology Department, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/ijc.33588","article-title":"Cancer statistics for the year 2020: An overview","volume":"149","author":"Ferlay","year":"2021","journal-title":"Int. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"239","DOI":"10.2147\/CMAR.S149619","article-title":"Gastric cancer: Epidemiology, prevention, classification, and treatment","volume":"10","author":"Sitarz","year":"2018","journal-title":"Cancer Manag. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1053\/j.gastro.2015.05.059","article-title":"Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma","volume":"149","author":"Tan","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/apm.1965.64.1.31","article-title":"The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma\u2014An attempt at a histo-clinical classification","volume":"64","author":"Lauren","year":"1965","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"ref_5","first-page":"S37","article-title":"Helicobacter pylori and gastric carcinogenesis","volume":"19","author":"Correa","year":"1995","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1056\/NEJMoa001999","article-title":"Helicobacter pylori infection and the development of gastric cancer","volume":"345","author":"Uemura","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/ajg.2009.728","article-title":"Pathology of gastric intestinal metaplasia: Clinical implications","volume":"105","author":"Correa","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/path.1246","article-title":"Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas","volume":"199","author":"Almeida","year":"2003","journal-title":"J. Pathol."},{"key":"ref_9","first-page":"1003","article-title":"Intestinal metaplasia of human stomach displays distinct patterns of mucin (MUC1, MUC2, MUC5AC, and MUC6) expression","volume":"59","author":"Reis","year":"1999","journal-title":"Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7318","DOI":"10.1073\/pnas.96.13.7318","article-title":"Reprogramming of intestinal differentiation and intercalary regeneration in Cdx2 mutant mice","volume":"96","author":"Beck","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ydbio.2009.12.025","article-title":"Cdx2 regulates patterning of the intestinal epithelium","volume":"339","author":"Grainger","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.molmed.2012.07.006","article-title":"Gastric intestinal metaplasia revisited: Function and regulation of CDX2","volume":"18","author":"Barros","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1053\/gast.2002.31902","article-title":"Cdx2 ectopic expression induces gastric intestinal metaplasia in transgenic mice","volume":"122","author":"Silberg","year":"2002","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/S0006-291X(02)00480-1","article-title":"Conversion of gastric mucosa to intestinal metaplasia in Cdx2-expressing transgenic mice","volume":"294","author":"Mutoh","year":"2002","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1101\/gad.348983.121","article-title":"Transcription factor-mediated intestinal metaplasia and the role of a shadow enhancer","volume":"36","author":"Singh","year":"2022","journal-title":"Genes. Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1083\/jcb.201207050","article-title":"MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression","volume":"200","author":"Zhu","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.4161\/cc.24602","article-title":"The novel actin\/focal adhesion-associated protein MISP is involved in mitotic spindle positioning in human cells","volume":"12","author":"Maier","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/gtc.12131","article-title":"Caprice\/MISP is a novel F-actin bundling protein critical for actin-based cytoskeletal reorganizations","volume":"19","author":"Kumeta","year":"2014","journal-title":"Genes. Cells"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"jcs214544","DOI":"10.1242\/jcs.214544","article-title":"Activated ezrin controls MISP levels to ensure correct NuMA polarization and spindle orientation","volume":"131","author":"Kschonsak","year":"2018","journal-title":"J. Cell Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Buenaventura, R.G.M., Merlino, G., and Yu, Y. (2023). Ez-Metastasizing: The Crucial Roles of Ezrin in Metastasis. Cells, 12.","DOI":"10.3390\/cells12121620"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"827051","DOI":"10.3389\/fonc.2022.827051","article-title":"Up-Regulated MISP Is Associated With Poor Prognosis and Immune Infiltration in Pancreatic Ductal Adenocarcinoma","volume":"12","author":"Huang","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8267021","DOI":"10.1155\/2019\/8267021","article-title":"Expression and Clinical Relevance of SOX9 in Gastric Cancer","volume":"2019","author":"Mesquita","year":"2019","journal-title":"Dis. Markers"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s10120-020-01064-6","article-title":"A panel of intestinal differentiation markers (CDX2, GPA33, and LI-cadherin) identifies gastric cancer patients with favourable prognosis","volume":"23","author":"Lopes","year":"2020","journal-title":"Gastric Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/s41417-023-00705-z","article-title":"PLK1 and its substrate MISP facilitate intrahepatic cholangiocarcinoma progression by promoting lymphatic invasion and impairing E-cadherin adherens junctions","volume":"31","author":"Pan","year":"2024","journal-title":"Cancer Gene Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hiura, K., Watanabe, M., Hirose, N., Nakano, K., Okamura, T., Sasaki, H., and Sasaki, N. (2024). Mitotic Spindle Positioning (MISP) Facilitates Colorectal Cancer Progression by Forming a Complex with Opa Interacting Protein 5 (OIP5) and Activating the JAK2-STAT3 Signaling Pathway. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25053061"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6330","DOI":"10.1038\/s41598-018-24682-8","article-title":"MISP regulates the IQGAP1\/Cdc42 complex to collectively orchestrate spindle orientation and mitotic progression","volume":"8","author":"Vodicska","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110848","DOI":"10.1016\/j.intimp.2023.110848","article-title":"Mechanism of M2 type macrophage-derived extracellular vesicles regulating PD-L1 expression via the MISP\/IQGAP1 axis in hepatocellular carcinoma immunotherapy resistance","volume":"124","author":"Wang","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1038\/s41467-021-23053-8","article-title":"Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer","volume":"12","author":"Shi","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"110692","DOI":"10.1016\/j.celrep.2022.110692","article-title":"Mitotic Spindle Positioning (MISP) is an actin bundler that selectively stabilizes the rootlets of epithelial microvilli","volume":"39","author":"Morales","year":"2022","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1292\/jvms.22-0483","article-title":"Mitotic spindle positioning protein (MISP) deficiency exacerbates dextran sulfate sodium (DSS)-induced colitis in mice","volume":"85","author":"Hiura","year":"2023","journal-title":"J. Vet. Med. Sci."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/5\/210\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:41:52Z","timestamp":1760107312000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/31\/5\/210"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,14]]},"references-count":30,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["curroncol31050210"],"URL":"https:\/\/doi.org\/10.3390\/curroncol31050210","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,14]]}}}