Cancer cell biology: mutated KRAS & reciprocal signalling скачать в хорошем качестве

Cancer cell biology: mutated KRAS & reciprocal signalling

Across a wide variety of cancer types, a protein called KRAS can get hyperactivated and transmit an overload of unwanted growth signals to the cells, causing them to divide and form a tumour. A tumour doesn't just contain cancer cells, though. It also has some non-cancer cells in there, such as immune cells and fibroblasts (cells that make the dense support structure that keeps cells stuck together). New research by Chris Tape, Claus Jørgensen and colleagues at The Institute of Cancer Research in London, MIT, the Cancer Research UK Manchester Institute and The University of Manchester, has shed some new light on how mutated KRAS causes cancer cells to grow by promoting three distinct ways of cellular signalling: 1) Through a direct signalling pathway within the cancer cell, with KRAS signalling through the classic RAS-RAF-MEK-ERK signal transduction cascade, this is called cell-autonomous signalling. 2) By inducing the cancer cell to release a protein called SHH, which is able to start specific signalling pathways inside the fibroblast cells. This is called non-cell-autonomous signalling. 3) When these non-cell-autonomous signalling pathways in the fibroblast cells are induced, the fibroblasts are able to release growth factors that go back to the cancer cell, where they initiate more growth signalling pathways through a PI3K-AKT signal transduction cascade. Uncovering these new ways in which mutated KRAS is able to promote cancer cell growth by hijacking fibroblast cell signalling could lead to new possibilities for therapeutic intervention. To find out more about this fascinating research, you can read Chris' blogpost here: http://christape.com/, and you can find Claus' lab page here: http://www.cruk.manchester.ac.uk/Rese... References: C.J. Tape, S. Ling, M. Dimitriadi, K.M. McMahon, J.D. Worboys, H.S. Leong, I.C. Norrie, C.J. Miller, G. Poulogiannis, D.A. Lauffenburger, C. Jørgensen, ‘Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation’, Cell (2016) 165(4) Tape, C.J., (2016) Systems Biology Analysis of Heterocellular Signaling, Trends in Biotechnology (2016) 34(8) Kolch, W., Halasz, M., Granovskaya, M., and Kholodenko, B.N. (2015). The dynamic control of signal transduction networks in cancer cells. Nat Rev Cancer 15, 515-527. Quail, D.F., and Joyce, J.A. (2013). Microenvironmental regulation of tumor progression and metastasis. Nature medicine 19, 1423- 1437. Friedl, P., and Alexander, S. (2011). Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 147, 992-1009.