Myotubularin-related protein 7 inhibits insulin signaling in colorectal cancer

• Verfasst von: Weidner, Philip [VerfasserIn]
• Verfasst von: Söhn, Michaela [VerfasserIn]
• Verfasst von: Gutting, Tobias [VerfasserIn]
• Verfasst von: Gaiser, Timo [VerfasserIn]
• Verfasst von: Kienle, Peter [VerfasserIn]
• Verfasst von: Ebert, Matthias [VerfasserIn]
• Verfasst von: Burgermeister, Elke [VerfasserIn]
• Titel: Myotubularin-related protein 7 inhibits insulin signaling in colorectal cancer
• Verf.angabe: Philip Weidner, Michaela Söhn, Tobias Gutting, Teresa Friedrich, Timo Gaiser, Julia Magdeburg, Peter Kienle, Hermelindis Ruh, Carsten Hopf, Hans-Michael Behrens, Christoph Röcken, Tamar Hanoch, Rony Seger, Matthias P.A. Ebert, Elke Burgermeister
• E-Jahr: 2016
• Jahr: July 07, 2016
• Umfang: 17 S.
• Fussnoten: Gesehen am 16.08.2019
• Titel Quelle: Enthalten in: OncoTarget
• Ort Quelle: [Erscheinungsort nicht ermittelbar] : Impact Journals LLC, 2010
• Jahr Quelle: 2016
• Band/Heft Quelle: 7(2016), 31, Seite 50490-50506
• ISSN Quelle: 1949-2553
• DOI: doi:10.18632/oncotarget.10466
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1671520033

Abstract

Phosphoinositide (PIP) phosphatases such as myotubularins (MTMs) inhibit growth factor receptor signaling. However, the function of myotubularin-related protein 7 (MTMR7) in cancer is unknown. We show that MTMR7 protein was down-regulated with increasing tumor grade (G), size (T) and stage (UICC) in patients with colorectal cancer (CRC) (n=1786). The presence of MTMR7 in the stroma correlated with poor prognosis, whereas MTMR7 expression in the tumor was not predictive for patients’ survival. Insulin reduced MTMR7 protein levels in human CRC cell lines, and CRC patients with type 2 diabetes mellitus (T2DM) or loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) had an increased risk for MTMR7 loss. Mechanistically, MTMR7 lowered PIPs and inhibited insulin-mediated AKT-ERK1/2 signaling and proliferation in human CRC cell lines. MTMR7 provides a novel link between growth factor signaling and cancer, and may thus constitute a potential marker or drug target for human CRC.