{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:51:55Z","timestamp":1790247115345,"version":"4.1.0"},"reference-count":40,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Among small GTPases from the Rho family, Cdc42, Rac, and Rho are well known to mediate a large variety of cellular processes linked with cancer biology through their ability to cycle between an inactive (GDP-bound) and an active (GTP-bound) state. Guanine nucleotide exchange factors (GEFs) stimulate the exchange of GDP for GTP to generate the activated form, whereas the GTPase-activating proteins (GAPs) catalyze GTP hydrolysis, leading to the inactivated form. Modulation of Rho GTPase activity following altered expression of Rho-GEFs and\/or Rho-GAPs has already been reported in various human tumors. However, nothing is known about the Rho GTPase activity or the expression of their regulators in human pheochromocytomas, a neuroendocrine tumor (NET) arising from chromaffin cells of the adrenal medulla. In this study, we demonstrate, through an ELISA-based activity assay, that Rac1 and Cdc42 activities decrease in human pheochromocytomas (PCCs) compared with the matched adjacent non-tumor tissue. Furthermore, through quantitative mass spectrometry (MS) approaches, we show that the expression of two Rho-GEF proteins, namely ARHGEF1 and FARP1, is significantly reduced in tumors compared with matched non-tumor tissue, whereas ARHGAP36 expression is increased. Moreover, siRNA-based knockdown of ARHGEF1 and FARP1 in PC12 cells leads to a significant inhibition of Rac1 and Cdc42 activities, respectively. Finally, a principal component analysis (PCA) of our dataset was able to discriminate PCC from non-tumor tissue and indicates a close correlation between Cdc42\/Rac1 activity and FARP1\/ARHGEF1 expression. Altogether, our findings reveal for the first time the importance of modulation of Rho GTPase activities and expression of their regulators in human PCCs.<\/jats:p>","DOI":"10.1530\/erc-15-0502","type":"journal-article","created":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T22:44:24Z","timestamp":1456353864000},"page":"281-293","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":25,"title":["Cdc42 and Rac1 activity is reduced in human pheochromocytoma and correlates with FARP1 and ARHGEF1 expression"],"prefix":"10.1530","volume":"23","author":[{"given":"Pauline","family":"Crois\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Houy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Gand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00ebl","family":"Lanoix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Calco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"T\u00f3th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Brunaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Lomazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eustache","family":"Paramithiotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Chelsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Ory","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Gasman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2016051819135692000_23.4.281.1","doi-asserted-by":"publisher","DOI":"10.4161\/sgtp.26530"},{"key":"2016051819135692000_23.4.281.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.11.010"},{"key":"2016051819135692000_23.4.281.3","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201205041"},{"key":"2016051819135692000_23.4.281.4","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2012"},{"key":"2016051819135692000_23.4.281.5","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.240"},{"key":"2016051819135692000_23.4.281.6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203259"},{"key":"2016051819135692000_23.4.281.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(03)00132-3"},{"key":"2016051819135692000_23.4.281.8","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-007-9119-1"},{"key":"2016051819135692000_23.4.281.9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1164"},{"key":"2016051819135692000_23.4.281.10","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E03-06-0402"},{"key":"2016051819135692000_23.4.281.11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.44.27374"},{"key":"2016051819135692000_23.4.281.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.73.7.2424"},{"key":"2016051819135692000_23.4.281.13","first-page":"137","article-title":"Rho GTPases in hepatocellular carcinoma","volume":"1795","author":"Grise","year":"2009","journal-title":"Biochimica et Biophysica Acta"},{"key":"2016051819135692000_23.4.281.14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.429746"},{"key":"2016051819135692000_23.4.281.15","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.226431"},{"key":"2016051819135692000_23.4.281.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2008.09.007"},{"key":"2016051819135692000_23.4.281.17","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2984"},{"key":"2016051819135692000_23.4.281.18","first-page":"91","article-title":"Rho GTPase function in tumorigenesis","volume":"1796","author":"Karlsson","year":"2009","journal-title":"Biochimica et Biophysica Acta"},{"key":"2016051819135692000_23.4.281.19","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M700354-MCP200"},{"issue":"Supplement A","key":"2016051819135692000_23.4.281.20","doi-asserted-by":"crossref","first-page":"S64","DOI":"10.1053\/joca.2001.0446","article-title":"Chondrocyte-derived ezrin-like domain containing protein (CDEP), a rho guanine nucleotide exchange factor, is inducible in chondrocytes by parathyroid hormone and cyclic AMP and has transforming activity in NIH3T3 cells","volume":"9","author":"Koyano Y","year":"2001","journal-title":"Osteoarthritis Cartilage"},{"key":"2016051819135692000_23.4.281.21","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7826"},{"key":"2016051819135692000_23.4.281.22","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"2016051819135692000_23.4.281.23","first-page":"287","article-title":"Gene expression abnormalities in human glial tumors identified by gene array","volume":"18","author":"Ljubimova","year":"2001","journal-title":"International Journal of Oncology"},{"key":"2016051819135692000_23.4.281.24","doi-asserted-by":"publisher","DOI":"10.1038\/nature00848"},{"key":"2016051819135692000_23.4.281.25","doi-asserted-by":"crossref","unstructured":"Orgaz JL Herraiz C Sanz-Moreno V 2014 Rho GTPases modulate malignant transformation of tumor cells. Small GTPases 5 e29019.","DOI":"10.4161\/sgtp.29019"},{"key":"2016051819135692000_23.4.281.26","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-8-23"},{"key":"2016051819135692000_23.4.281.27","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1322362111"},{"key":"2016051819135692000_23.4.281.28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00121.x"},{"key":"2016051819135692000_23.4.281.29","doi-asserted-by":"publisher","DOI":"10.1021\/pr800389e"},{"key":"2016051819135692000_23.4.281.30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2007.01164.x"},{"key":"2016051819135692000_23.4.281.31","doi-asserted-by":"publisher","DOI":"10.1159\/000080731"},{"key":"2016051819135692000_23.4.281.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2013.12.009"},{"key":"2016051819135692000_23.4.281.33","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1158\/0008-5472.CAN-04-2469","article-title":"Inhibition of a new differentiation pathway in neuroblastoma by copy number defects of N-myc, Cdc42, and nm23 genes","volume":"65","author":"Valentijn","year":"2005","journal-title":"Cancer Research"},{"key":"2016051819135692000_23.4.281.34","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.002"},{"key":"2016051819135692000_23.4.281.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.04.039"},{"key":"2016051819135692000_23.4.281.36","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2960"},{"key":"2016051819135692000_23.4.281.37","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-03-079582"},{"key":"2016051819135692000_23.4.281.38","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.15.4377"},{"key":"2016051819135692000_23.4.281.39","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2916"},{"key":"2016051819135692000_23.4.281.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.12.022"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/23\/4\/281.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/23\/4\/281.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:53:26Z","timestamp":1784555606000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/erc\/article\/23\/4\/281-293\/34087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":40,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.1530\/erc-15-0502","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4]]}}}