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Raf-1 Addiction in Ras-Induced Skin Carcinogenesis

Autor(en)

Karin Ehrenreiter, Florian Kern, Vanishree Velamoor, Katrin Meissl, Gergana Galabova-Kovacs, Maria Sibilia, Manuela Baccarini

Abstrakt

Ras activation is common to many human cancers and promotes cell proliferation and survival by initiating

multiple signaling cascades. Accordingly, Ras-transformed cells are generally considered too resourceful to

become addicted to a single effector. In contrast to this tenet, we now demonstrate an absolute, cell autonomous

requirement for Raf-1 in the development and maintenance of Ras-induced skin epidermis tumors.

Mechanistically, Raf-1 functions as an endogenous inhibitor dimming the activity of the Rho-dependent

kinase Rok-a in the context of a Ras-induced Raf-1:Rok-a complex. Raf-1-induced Rok-a inhibition allows

the phosphorylation of STAT3 and Myc expression and promotes dedifferentiation in Ras-induced tumors.

These data link the Raf-1:Rok-a complex to STAT3/Myc activation and delineate a pathway crucial for cell

fate decision in Ras-induced tumorigenesis.

Organisation(en)

Department für Mikrobiologie, Immunbiologie und Genetik, Department für Biochemie und Zellbiologie

Externe Organisation(en)

Max F. Perutz Laboratories GmbH (MFPL)

Journal

Cancer Cell

Band

Seiten

149-160

Anzahl der Seiten

ISSN

1535-6108

Publikationsdatum

2009

Peer-reviewed

ÖFOS 2012

106002 Biochemie, 106052 Zellbiologie, 106013 Genetik, 106023 Molekularbiologie

Sustainable Development Goals

SDG 3 – Gesundheit und Wohlergehen

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