{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:51:09Z","timestamp":1775019069550,"version":"3.50.1"},"reference-count":106,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,5]],"date-time":"2021-06-05T00:00:00Z","timestamp":1622851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Science, Innovation and Universities","award":["RTI2018-094629-B-I0"],"award-info":[{"award-number":["RTI2018-094629-B-I0"]}]},{"name":"European Comission","award":["TRIBBLES \u2013 748585"],"award-info":[{"award-number":["TRIBBLES \u2013 748585"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["PTDC\/MED-ONC\/4167\/2020 \u201cENDURING\u201d"],"award-info":[{"award-number":["PTDC\/MED-ONC\/4167\/2020 \u201cENDURING\u201d"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The Tribbles family of pseudokinases controls a wide number of processes during cancer on-set and progression. However, the exact contribution of each of the three family members is still to be defined. Their function appears to be context-dependent as they can act as oncogenes or tumor suppressor genes. They act as scaffolds modulating the activity of several signaling pathways involved in different cellular processes. In this review, we discuss the state-of-knowledge for TRIB1, TRIB2 and TRIB3 in the development and progression of colorectal cancer. We take a perspective look at the role of Tribbles proteins as potential biomarkers and therapeutic targets. Specifically, we chronologically systematized all available articles since 2003 until 2020, for which Tribbles were associated with colorectal cancer human samples or cell lines. Herein, we discuss: (1) Tribbles amplification and overexpression; (2) the clinical significance of Tribbles overexpression; (3) upstream Tribbles gene and protein expression regulation; (4) Tribbles pharmacological modulation; (5) genetic modulation of Tribbles; and (6) downstream mechanisms regulated by Tribbles; establishing a comprehensive timeline, essential to better consolidate the current knowledge of Tribbles\u2019 role in colorectal cancer.<\/jats:p>","DOI":"10.3390\/cancers13112825","type":"journal-article","created":{"date-parts":[[2021,6,6]],"date-time":"2021-06-06T23:59:55Z","timestamp":1623023995000},"page":"2825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Tribbles Pseudokinases in Colorectal Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Bibiana I.","family":"Ferreira","sequence":"first","affiliation":[{"name":"Centre for Biomedical Research (CBMR), Campus of Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center (ABC), Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Faculdade de Medicina e Ci\u00eancias Biom\u00e9dicas (FMCB), Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal"}]},{"given":"Bruno","family":"Santos","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research (CBMR), Campus of Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center (ABC), Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Servi\u00e7o de Anatomia Patol\u00f3gica, Centro Hospital Universit\u00e1rio do Algarve (CHUA), 8000-386 Faro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3340-5165","authenticated-orcid":false,"given":"Wolfgang","family":"Link","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM), Arturo Duperier 4, 28029 Madrid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8451-4302","authenticated-orcid":false,"given":"Ana Lu\u00edsa","family":"De Sousa-Coelho","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research (CBMR), Campus of Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Algarve Biomedical Center (ABC), Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal"},{"name":"Escola Superior de Sa\u00fade (ESS), Campus de Gambelas, Universidade do Algarve, 8005-139 Faro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,5]]},"reference":[{"key":"ref_1","unstructured":"International Agency for Research on Cancer (IARC) (2021, April 21). 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