(Wilhelminenspital Medizinische Abteilung, Wien, Austria); Markus Heim, M.D. (Universitätsspital Basel-Medizinische Klinik, Basel, Switzerland); Ming-Yang Lai, M.D. (National Taiwan University Hospital, Taipei, Taiwan); Eric Lawitz, M.D. (Alamo Medical Research, San Antonio, TX); Yoav Lurie, M.D. (Gastrointestinal and Liver Disease Unit, Sourasky Medical Center, Tel Aviv, Israel); Darius Moradpour,
M.D. (Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland); Beat Müllhaupt, M.D. DNA Damage inhibitor (Universitätsspital Zürich, Zürich, Switzerland); Francesco Negro, M.D. (Hôpitaux Universitaires, Genéve, Switzerland); Court Pedersen, M.D. (Odense Universitets Hospital, Odense, Denmark); Ramón Planas Vila, M.D. (H. de Badalona Germans Trias I Pujol, Barcelona, Spain); Mark Russo, M.D. (Carolinas Medical Center, Charlotte, NC); Rifaat Safadi, M.D. (Liver Unit, Italian [Holy Family] Hospital, Nazareth, Israel); Alejandro Soza, M.D. (Hospital de la Pontificia Universidad
Catolica, Hepatologia, Santiago, Chile); Ulrich Spengler, M.D. (Rheinische Friedrich-Wilhelms-Universitaet Bonn, Bonn, Germany); Rudolf Stauber, M.D. (MedUni Graz, Klinische Abteilung für Gastroenterologie und Hepatologie, Graz, Austria); Petr Urbanek, M.D. (Hepato-gastro-enterologie, Hradec Kralove, BYL719 chemical structure Czech Republic); Elena Volchkova, M.D. (Clinical Hospital of Infectious Diseases #2, Moscow, Russian Federation); Miroslava Volfova, M.D. (Klin Med s.r.o., Praha, Czech Republic); Stefan Zeuzem, M.D. (Klinikum der Johann-Wolfgang-Goethe-Universitaet, Frankfurt,
Germany). Additional Supporting Information may be found in the online version of this article. “
“It is unclear how proliferating cells elicit suppression PAK5 on cell proliferation and how cancer cells evade this growth suppression. Using a loss-of-function screening of the human kinome and phosphatome to identify genes suppressing tumor initiation in human hepatocellular carcinoma (HCC), we identified 19 genes and characterized one of the top-scoring tumor suppressor candidates, protein tyrosine phosphatase receptor type F (PTPRF). We found that PTPRF was induced during cell proliferation by cell-cell contact. Ectopic expression of wild-type PTPRF, but not the phosphatase-inactive mutant, suppressed cell proliferation and colony formation in soft-agar assays. In contrast, PTPRF silencing led to cell hyperproliferation, enhanced tumor colony formation in soft agar, and increased xenograft tumor growth in nude mice. Mechanistically, PTPRF silencing showed aberrant ERK-dependent signaling including the phosphorylation/stabilization of v-myc avian myelocytomatosis viral oncogene homolog (MYC) through the direct activation of v-src avian sarcoma viral oncogene homolog (SRC) and suppression of PP2A. This PTPRF-mediated growth suppression during cell proliferation functioned independently of the Hippo-Yap pathway. Clinically, PTPRF was down-regulated in 42% HCC (37/89), 67% gastric cancer (27/40), and 100% colorectal cancer (40/40).