{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:09:00Z","timestamp":1788930540657,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006447","name":"Universit\u00e4t Z\u00fcrich","doi-asserted-by":"publisher","award":["UZH STEB-21-005"],"award-info":[{"award-number":["UZH STEB-21-005"]}],"id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"publisher"}]},{"award":["UZH STEB-21-005"],"award-info":[{"award-number":["UZH STEB-21-005"]}],"id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"SNSF","doi-asserted-by":"publisher","award":["215022"],"award-info":[{"award-number":["215022"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"award":["215022"],"award-info":[{"award-number":["215022"]}],"id":[{"id":"https:\/\/ror.org\/00yjd3n13","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008479","name":"Julius-M\u00fcller Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008479","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Protein tyrosine phosphatases (PTPs) are key regulators of intracellular signaling cascades involved in cell growth, proliferation, differentiation, inflammation, and cancer. PTPN23, a non-receptor PTP, is involved in endosomal sorting and thereby regulates the internalization of growth factor receptors, such as the epidermal growth factor receptor (EGFR). PTPN23 has been proposed to exert tumor-suppressive effects in several epithelial cancers, including breast and lung cancer. PTPN23 is ubiquitously expressed in the body; however, it is particularly highly expressed in the intestine, where it plays an essential role in maintaining intestinal homeostasis. Despite these observations, its involvement in colorectal carcinoma (CRC) remains largely unexplored. To investigate the function of PTPN23 in CRC, we generated PTPN23-overexpressing CRC cell lines and evaluated their effects in vitro and in subcutaneous tumor models. Our in-vitro findings demonstrate that PTPN23 overexpression resulted in reduced proliferation levels and follow-up experiments showed suppression of colorectal cancer growth and proliferation in experimental CRC models. These effects were accompanied by changes in EGFR-associated signaling; however, the underlying mechanism, including a potential role of EGFR trafficking, remains to be established through direct experimental validation. Together, these findings expand current knowledge of PTPN23 in colorectal cancer and provide a basis for future studies addressing its biological function and therapeutic relevance.<\/jats:p>","DOI":"10.3390\/ijms27177955","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"7955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PTPN23 Overexpression Is Associated with Reduced Proliferation and Tumor Growth in Murine Models of Colorectal Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3801-0441","authenticated-orcid":false,"given":"Rocio","family":"Sanchez Alvarez","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6045-0228","authenticated-orcid":false,"given":"Claudia","family":"Gottier","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4700-4263","authenticated-orcid":false,"given":"Ana","family":"Montalban-Arques","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4207-0968","authenticated-orcid":false,"given":"Anna","family":"Bircher","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8835-5210","authenticated-orcid":false,"given":"Doris","family":"P\u00f6hlmann","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1288-0706","authenticated-orcid":false,"given":"Marlene","family":"Schwarzfischer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Anne","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research, University of Zurich, 8057 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1216-899X","authenticated-orcid":false,"given":"Silvia","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4498-0058","authenticated-orcid":false,"given":"Marianne R.","family":"Spalinger","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Michael","family":"Scharl","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1159\/000502861","article-title":"Loss of PTPN23 Promotes Proliferation and Epithelial-to-Mesenchymal Transition in Human Intestinal Cancer Cells","volume":"4","author":"Schwarzfischer","year":"2019","journal-title":"Inflamm. Intest. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1387\/ijdb.082820mg","article-title":"Expression analysis and essential role of the putative tyrosine phosphatase His-domain-containing protein tyrosine phosphatase (HD-PTP)","volume":"53","author":"Gingras","year":"2009","journal-title":"Int. J. Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1016\/j.celrep.2016.04.076","article-title":"Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer","volume":"15","author":"Manteghi","year":"2016","journal-title":"Cell Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10364","DOI":"10.1038\/s41467-024-54749-2","article-title":"PTPN23-dependent ESCRT machinery functions as a cell death checkpoint","volume":"15","author":"Song","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"a016949","DOI":"10.1101\/cshperspect.a016949","article-title":"Endocytosis and cancer","volume":"5","author":"Mellman","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.cub.2013.02.033","article-title":"Recruitment of UBPY and ESCRT exchange drive HD-PTP-dependent sorting of EGFR to the MVB","volume":"23","author":"Ali","year":"2013","journal-title":"Curr. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/1878-0261.12155","article-title":"Emerging functions of the EGFR in cancer","volume":"12","author":"Sigismund","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"jjaf016","DOI":"10.1093\/ecco-jcc\/jjaf016","article-title":"Intestinal epithelial PTPN23 is essential for gut barrier integrity and prevention of fatal bacterial translocation","volume":"19","author":"Morsy","year":"2025","journal-title":"J. Crohns Colitis"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.4251\/wjgo.v16.i4.1119","article-title":"Colorectal cancer screening: A review of current knowledge and progress in research","volume":"16","author":"Lopes","year":"2024","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.rpor.2017.12.003","article-title":"Adenomas\u2014Genetic factors in colorectal cancer prevention","volume":"23","author":"Witold","year":"2018","journal-title":"Rep. Pract. Oncol. Radiother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1038\/s41577-021-00534-x","article-title":"The inflammatory pathogenesis of colorectal cancer","volume":"21","author":"Schmitt","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sivaganesh, V., Sivaganesh, V., Scanlon, C., Iskander, A., Maher, S., L\u00ea, T., and Peethambaran, B. (2021). Protein Tyrosine Phosphatases: Mechanisms in Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312865"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1038\/s43018-024-00807-z","article-title":"Integrative single-cell analysis of human colorectal cancer reveals patient stratification with distinct immune evasion mechanisms","volume":"5","author":"Chu","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1091\/mbc.E14-06-1151","article-title":"The catalytically inactive tyrosine phosphatase HD-PTP\/PTPN23 is a novel regulator of SMN complex localization","volume":"26","author":"Husedzinovic","year":"2015","journal-title":"Mol. Biol. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19980","DOI":"10.1038\/s41598-024-70358-x","article-title":"In vitro evidence for the potential of EGFR inhibitors to decrease the TGF-\u03b21-induced dispersal of circulating tumour cell clusters mediated by EGFR overexpression","volume":"14","author":"Hapeman","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7530","DOI":"10.3390\/cimb46070447","article-title":"Erlotinib Treatment in Colorectal Cancer Suppresses Autophagy Based on KRAS Mutation","volume":"46","author":"Siegman","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"932932","DOI":"10.4061\/2011\/932932","article-title":"EGFR Signaling in Colorectal Carcinoma","volume":"2011","author":"Krasinskas","year":"2011","journal-title":"Pathol. Res. Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/annonc\/mdm492","article-title":"EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients","volume":"19","author":"Cappuzzo","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1111\/febs.12393","article-title":"The epidermal growth factor receptor variant III (EGFRvIII): Where wild things are altered","volume":"280","author":"Gan","year":"2013","journal-title":"FEBS J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.eururo.2012.05.033","article-title":"Combination of CK20 and Ki-67 Immunostaining Analysis Predicts Recurrence, Progression, and Cancer-Specific Survival in pT1 Urothelial Bladder Cancer","volume":"65","author":"Bertz","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_21","first-page":"1175","article-title":"Low-level Ki-67 expression as an independent predictor of bladder tumour recurrence in patients with primary upper tract urothelial carcinoma after radical nephroureterectomy","volume":"45","author":"Wu","year":"2015","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"ra45","DOI":"10.1126\/scisignal.2004015","article-title":"AKT facilitates EGFR trafficking and degradation by phosphorylating and activating PIKfyve","volume":"6","author":"Er","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/s41580-020-0255-7","article-title":"ERK signalling: A master regulator of cell behaviour, life and fate","volume":"21","author":"Lavoie","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_24","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo","year":"2020","journal-title":"Exp. Ther. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41417-020-0200-0","article-title":"ESCRT-III-mediated membrane repair in cell death and tumor resistance","volume":"28","author":"Liu","year":"2021","journal-title":"Cancer Gene Ther."},{"key":"ref_26","first-page":"95","article-title":"An improved method for increasing the efficiency of gene transfection and transduction","volume":"10","author":"Shi","year":"2018","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"429","DOI":"10.4103\/1947-2714.100998","article-title":"Western blot: Technique, theory, and trouble shooting","volume":"4","author":"Mahmood","year":"2012","journal-title":"N. Am. J. Med. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e140281","DOI":"10.1172\/JCI140281","article-title":"Protein tyrosine phosphatase nonreceptor type 2 controls colorectal cancer development","volume":"131","author":"Katkeviciute","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/s41568-024-00763-x","article-title":"The present and future of the Cancer Dependency Map","volume":"25","author":"Arafeh","year":"2025","journal-title":"Nat. Rev. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"W556","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An enhanced web server for large-scale expression profiling and interactive analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7955\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:23:11Z","timestamp":1788927791000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7955"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":31,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177955"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177955","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}