Abstract
The non-receptor tyrosine kinase Fyn-related kinase (FRK) is a member of the BRK family kinases (BFKs) and is distantly related to the Src family kinases (SFKs). FRK was first discovered in 1993, and studies pursued thereafter attributed a potential tumour-suppressive function to the enzyme. In recent years, however, further functional characterization of the tyrosine kinase in diverse cancer types suggests that FRK may potentially play an oncogenic role as well. Specifically, while ectopic expression of FRK suppresses cell proliferation and migration in breast and brain cancers, knockdown or catalytic inhibition of FRK suppresses these cellular processes in pancreatic and liver cancer. Such functional paradox is therefore evidently exhibited in a tissue-specific context. This review sheds light on the recent developments emerged from investigations on FRK which include: (a) a review of the expression pattern of the protein in mammalian cells/tissues, (b) underlying genomic perturbations and (c) a mechanistic function of the enzyme across different cellular environments. Given its functional heterogeneity observed across different cancers, we also discuss the therapeutic significance of FRK.
Keywords:
BFKs; BRK; Breast cancer; FRK; Fyn; Oncogene; PTEN; PTK5; Rak; SRMS; Src; Tumour suppressor; Tyrosine kinase.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
Animals, Genetically Modified
-
Antineoplastic Agents / pharmacology
-
Cell Nucleus / metabolism
-
Cell Proliferation
-
Cell Transformation, Neoplastic / genetics
-
Cell Transformation, Neoplastic / metabolism
-
Chromosome Aberrations
-
Disease Models, Animal
-
Enzyme Activation
-
Gene Expression Regulation, Neoplastic
-
Humans
-
Molecular Targeted Therapy
-
Mutation
-
Neoplasm Metastasis
-
Neoplasm Proteins / chemistry
-
Neoplasm Proteins / genetics*
-
Neoplasm Proteins / metabolism*
-
Neoplasms / drug therapy
-
Neoplasms / genetics*
-
Neoplasms / metabolism*
-
Neoplasms / pathology
-
Protein Binding
-
Protein Conformation
-
Protein Kinase Inhibitors / pharmacology
-
Protein Kinase Inhibitors / therapeutic use
-
Protein Transport
-
Protein-Tyrosine Kinases / chemistry
-
Protein-Tyrosine Kinases / genetics*
-
Protein-Tyrosine Kinases / metabolism*
-
Signal Transduction
-
Structure-Activity Relationship
-
Substrate Specificity
-
Tumor Suppressor Proteins / chemistry
-
Tumor Suppressor Proteins / genetics
-
Tumor Suppressor Proteins / metabolism
-
src-Family Kinases / chemistry
-
src-Family Kinases / genetics
-
src-Family Kinases / metabolism
Substances
-
Antineoplastic Agents
-
Neoplasm Proteins
-
Protein Kinase Inhibitors
-
Tumor Suppressor Proteins
-
Protein-Tyrosine Kinases
-
FRK protein, human
-
src-Family Kinases