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Myeloid cell leukemia 1 (MCL-1), an unexpected modulator of protein kinase signaling during invasion


Myeloid cell leukemia-1 (MCL-1), closely related to B-cell lymphoma 2 (BCL-2), has a well-established role in cell survival and has emerged as an important target for cancer therapeutics. We have demonstrated that inhibiting MCL-1 is efficacious in suppressing tumour progression in pre-clinical models of breast cancer and revealed that in addition to its role in cell survival, MCL-1 modulated cellular invasion. Utilizing a MCL-1-specific genetic antagonist, we found two possible mechanisms; firstly MCL-1 directly binds to and alters the phosphorylation of the cytoskeletal remodeling protein, Cofilin, a protein important for cytoskeletal remodeling during invasion, and secondly MCL-1 modulates the levels SRC family kinases (SFKs) and their targets. These data provide evidence that MCL-1 activities are not limited to endpoints of extracellular and intracellular signaling culminating in cell survival as previously thought, but can directly modulate the output of SRC family kinases signaling during cellular invasion. Here we review the pleotropic roles of MCL-1 and discuss the implications of this newly discovered effect on protein kinase signaling for the development of cancer therapeutics.

Type Journal
ISBN 1933-6926 (Electronic) 1933-6918 (Linking)
Authors Young, A. I.; Timpson, P.; Gallego-Ortega, D.; Ormandy, C. J.; Oakes, S. R.
Responsible Garvan Author Dr Samantha Oakes
Publisher Name Cell Adhesion & Migration
Published Date 2018-12-31
Published Volume 12
Published Issue 6
Published Pages 513-523
Status Published in-print
DOI 10.1080/19336918.2017.1393591
URL link to publisher's version