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However, the interrelation of the ERK1\/2 module relative to other signalling pathways in intestinal epithelial cells and colorectal cancer (CRC) is unclear. Here we show that loss of\n                    <jats:italic>Erk1<\/jats:italic>\n                    \/\n                    <jats:italic>2<\/jats:italic>\n                    in intestinal epithelial cells results in defects in nutrient absorption, epithelial cell migration and secretory cell differentiation. However, intestinal epithelial cell proliferation is not impeded, implying compensatory mechanisms. Genetic deletion of\n                    <jats:italic>Erk1\/2<\/jats:italic>\n                    or pharmacological targeting of MEK1\/2 results in supraphysiological activity of the ERK5 pathway. Furthermore, targeting both pathways causes a more effective suppression of cell proliferation in murine intestinal organoids and human CRC lines. These results suggest that ERK5 provides a common bypass route in intestinal epithelial cells, which rescues cell proliferation upon abrogation of ERK1\/2 signalling, with therapeutic implications in CRC.\n                  <\/jats:p>","DOI":"10.1038\/ncomms11551","type":"journal-article","created":{"date-parts":[[2016,5,17]],"date-time":"2016-05-17T09:11:34Z","timestamp":1463476294000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["ERK5 signalling rescues intestinal epithelial turnover and tumour cell proliferation upon ERK1\/2 abrogation"],"prefix":"10.1038","volume":"7","author":[{"given":"Petrus R.","family":"de Jong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra R.","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Bertin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen","family":"Duong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro D.","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth","family":"Powis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maripat","family":"Corr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Karin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eyal","family":"Raz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,17]]},"reference":[{"key":"BFncomms11551_CR1","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1128\/MMBR.68.2.320-344.2004","volume":"68","author":"PP Roux","year":"2004","unstructured":"Roux, P. 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