PMID- 31717606 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 11 IP - 11 DP - 2019 Nov 9 TI - DUSP10 Is a Regulator of YAP1 Activity Promoting Cell Proliferation and Colorectal Cancer Progression. LID - 10.3390/cancers11111767 [doi] LID - 1767 AB - Cell contact inhibition (CCI) is deregulated in cancer. Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. We found that dual-specificity phosphatase 10 (DUSP10) is involved in CRC. DUSP10 overexpression increased the growth of CRC cell lines and mouse xenografts, while the opposite phenotype was observed by DUSP10 silencing. High cell density (HD) induced DUSP10 expression in CRC cell lines, particularly within the nucleus. Yes-associated protein 1 (YAP1) is activated by dephosphorylation, controlling organ growth and CCI, both processes being deregulated in CRC. Expression levels and localization of DUSP10 matched with YAP1 levels in CRC cell lines. DUSP10 and YAP1 co-immunoprecipitated and their interaction was dependent on YAP1 Ser397. The existence of DUSP10 and YAP1 pathway in vivo was confirmed by using a transgenic Drosophila model. Finally, in CRC patients' samples, high levels of nuclear DUSP10 correlated with nuclear YAP1 in epithelial tumor tissue. Strong nuclear DUSP10 staining also correlated with high tumor stage and poor survival. Overall, these findings describe a DUSP10-YAP1 molecular link in CRC cell lines promoting cell growth in HD. We present evidence suggesting a pro-tumorigenic role of nuclear DUSP10 expression in CRC patients. FAU - Jimenez-Martinez, Marta AU - Jimenez-Martinez M AD - Department of Cell Biology and Immunology, Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), 28049 Madrid, Spain. AD - Department of Molecular Biology, Universidad Autonoma de Madrid (UAM), 28049 Madrid, Spain. AD - Instituto de Investigacion Sanitaria de La Princesa (IIS-P), 28006 Madrid, Spain. FAU - Ostale, Cristina M AU - Ostale CM AD - Department of Development and Regeneration, Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), 28049 Madrid, Spain. FAU - van der Burg, Lennart R AU - van der Burg LR AD - Department of Gastroenterology-Hepatology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. FAU - Galan-Martinez, Javier AU - Galan-Martinez J AD - Department of Cell Biology and Immunology, Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), 28049 Madrid, Spain. AD - Department of Molecular Biology, Universidad Autonoma de Madrid (UAM), 28049 Madrid, Spain. AD - Instituto de Investigacion Sanitaria de La Princesa (IIS-P), 28006 Madrid, Spain. FAU - Hardwick, James C H AU - Hardwick JCH AD - Department of Gastroenterology-Hepatology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. FAU - Lopez-Perez, Ricardo AU - Lopez-Perez R AUID- ORCID: 0000-0001-9495-8604 AD - Department of Cell Biology and Immunology, Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), 28049 Madrid, Spain. FAU - Hawinkels, Lukas J A C AU - Hawinkels LJAC AUID- ORCID: 0000-0002-2274-9325 AD - Department of Gastroenterology-Hepatology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands. FAU - Stamatakis, Konstantinos AU - Stamatakis K AUID- ORCID: 0000-0001-9934-3502 AD - Department of Cell Biology and Immunology, Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), 28049 Madrid, Spain. AD - Department of Molecular Biology, Universidad Autonoma de Madrid (UAM), 28049 Madrid, Spain. AD - Instituto de Investigacion Sanitaria de La Princesa (IIS-P), 28006 Madrid, Spain. FAU - Fresno, Manuel AU - Fresno M AD - Department of Cell Biology and Immunology, Centro de Biologia Molecular "Severo Ochoa" (CSIC-UAM), 28049 Madrid, Spain. AD - Department of Molecular Biology, Universidad Autonoma de Madrid (UAM), 28049 Madrid, Spain. AD - Instituto de Investigacion Sanitaria de La Princesa (IIS-P), 28006 Madrid, Spain. LA - eng GR - SAF2013-42850-R/Ministerio de Ciencia e Innovacion/ GR - SAF2016-75988-R/Ministerio de Ciencia e Innovacion/ GR - S2017/BMD-3671/Comunidad de Madrid/ GR - BIOMID/Fondo de investigaciones Sanitarias La Princesa/ GR - AIO/Fundacion Cientifica Asociacion Espanola Contra el Cancer/ PT - Journal Article DEP - 20191109 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC6896144 OTO - NOTNLM OT - cancer OT - cell contact inhibition OT - cell proliferation OT - prognosis OT - protein COIS- The authors declare no conflict of interest. EDAT- 2019/11/14 06:00 MHDA- 2019/11/14 06:01 PMCR- 2019/11/09 CRDT- 2019/11/14 06:00 PHST- 2019/10/18 00:00 [received] PHST- 2019/10/31 00:00 [revised] PHST- 2019/11/05 00:00 [accepted] PHST- 2019/11/14 06:00 [entrez] PHST- 2019/11/14 06:00 [pubmed] PHST- 2019/11/14 06:01 [medline] PHST- 2019/11/09 00:00 [pmc-release] AID - cancers11111767 [pii] AID - cancers-11-01767 [pii] AID - 10.3390/cancers11111767 [doi] PST - epublish SO - Cancers (Basel). 2019 Nov 9;11(11):1767. doi: 10.3390/cancers11111767.