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

Young, AI; Timpson, P; Gallego-Ortega, D; Ormandy, CJ; Oakes, SR

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

Young, AI Timpson, P Gallego-Ortega, D Ormandy, CJ Oakes, SR

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Publisher:: TAYLOR & FRANCIS INC
Publication Type:: Journal Article
Citation:: Cell Adh Migr, 2018, 12, (6), pp. 513-523
Issue Date:: 2018

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Field	Value	Language
dc.contributor.author	Young, AI
dc.contributor.author	Timpson, P
dc.contributor.author	Gallego-Ortega, D
dc.contributor.author	Ormandy, CJ
dc.contributor.author	Oakes, SR
dc.date.accessioned	2022-04-13T12:23:19Z
dc.date.available	2022-04-13T12:23:19Z
dc.date.issued	2018
dc.identifier.citation	Cell Adh Migr, 2018, 12, (6), pp. 513-523
dc.identifier.issn	1933-6918
dc.identifier.issn	1933-6926
dc.identifier.uri	http://hdl.handle.net/10453/156214
dc.description.abstract	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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	TAYLOR & FRANCIS INC
dc.relation.ispartof	Cell Adh Migr
dc.relation.isbasedon	10.1080/19336918.2017.1393591
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0601 Biochemistry and Cell Biology, 0699 Other Biological Sciences
dc.subject.classification	Developmental Biology
dc.subject.mesh	Animals
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Cell Survival
dc.subject.mesh	Humans
dc.subject.mesh	Myeloid Cell Leukemia Sequence 1 Protein
dc.subject.mesh	Myeloid Cells
dc.subject.mesh	Protein Kinases
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Myeloid Cells
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Breast Neoplasms
dc.subject.mesh	Protein Kinases
dc.subject.mesh	Signal Transduction
dc.subject.mesh	Cell Survival
dc.subject.mesh	Myeloid Cell Leukemia Sequence 1 Protein
dc.title	Myeloid cell leukemia 1 (MCL-1), an unexpected modulator of protein kinase signaling during invasion.
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	United States
utslib.for	0601 Biochemistry and Cell Biology
utslib.for	0699 Other Biological Sciences
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Centre for Health Technologies (CHT)
utslib.copyright.status	open_access	*
dc.date.updated	2022-04-13T12:23:16Z
pubs.issue	6
pubs.publication-status	Published
pubs.volume	12
utslib.citation.issue	6

Abstract:

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.

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http://hdl.handle.net/10453/156214