{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:58:52Z","timestamp":1790989132534,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Japan Society for the Promotion of Science KAKENHI","award":["JP20K16311"],"award-info":[{"award-number":["JP20K16311"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Japan Society for the Promotion of Science KAKENHI","award":["2633\u00a0K2738"],"award-info":[{"award-number":["2633\u00a0K2738"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Genetic and epigenetic alterations in colorectal cancer (CRC) have been extensively investigated. Small depressed-type colorectal tumours (DCs) constitute a highly invasive CRC subtype. We characterized the mutational profiles of 22\u00a0DC samples, seven of which were subjected to whole exome sequencing. This revealed frequent mutations (7 of 22 cases, 31.8%) in PTPRK, with most of these mutations located in the D1 domain-encoding region. To further quantify the incidence of PTPRK mutations, we analysed 567 CRCs cases from two public databases (The Cancer Genome Atlas and the Catalogue of Somatic Mutations in Cancer). Mutations were more frequently observed in proximal colon tumours and were highly associated with the CpG island methylator phenotype-positive (CIMP-P) subtype (76.2%) and microsatellite instability (MSI; 66.7%). PTPRK mutant proteins (particularly those with D1 domain) retained the ability to bind integrin beta-4 (ITGB4). In addition, CRC cells expressing PTPRK mutants exhibited increased ITGB4 phosphorylation, suggesting that the mutations impair the phosphatase activity of PTPRK. Consistent with this, tumours with PTPRK mutations proliferated significantly more rapidly than their wild-type counterparts in vivo. These findings suggest that PTPRK mutations contribute to DC development by dysregulating phosphorylation-mediated signalling pathways.<\/jats:p>","DOI":"10.1093\/jb\/mvag024","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T12:53:18Z","timestamp":1773233598000},"page":"49-63","source":"Crossref","is-referenced-by-count":0,"title":["Recurrent mutations in protein tyrosine phosphatase receptor-type kappa in depressed-type colorectal carcinomas"],"prefix":"10.1093","volume":"180","author":[{"given":"Masayuki","family":"Tojo","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Showa Medical University School of Medicine , 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7797-6453","authenticated-orcid":false,"given":"Keiko","family":"Shinjo","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5569-5626","authenticated-orcid":false,"given":"Fumiharu","family":"Ohka","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 ,","place":["Japan"]},{"name":"Department of Neurosurgery, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Katsushima","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Hatanaka","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihisa","family":"Ichimura","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 ,","place":["Japan"]},{"name":"Department of Oral and Maxillofacial Surgery, Komaki City Hospital , 1-20 Jobushin, Komaki City, 485-8520 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology, Department of Biochemistry, Sapporo Medical University , 17, Minami-1-jonishi, Chuo-ku, Sapporo City, 060-8556 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisako","family":"Nozawa","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Showa Medical University School of Medicine , 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Showa Medical University School of Medicine , 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Konishi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Showa Medical University School of Medicine , 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Kondo","sequence":"additional","affiliation":[{"name":"Division of Cancer Biology, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"2026100220312978400_ref1","first-page":"233","article-title":"Colorectal cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. 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