Mechanisms of HGF/Met signaling to Brk and Sam68 in breast cancer progression

Horm Cancer. 2012 Apr;3(1-2):14-25. doi: 10.1007/s12672-011-0097-z.

Abstract

Signal transduction pathways downstream of receptor tyrosine kinases (RTKs) are often deregulated during oncogenesis, tumor progression, and metastasis. In particular, the peptide growth factor hormone, hepatocyte growth factor (HGF), and its specific receptor, Met tyrosine kinase, regulate cancer cell migration, thereby conferring an aggressive phenotype (Nakamura et al., J Clin Invest 106(12):1511-1519, 2000; Huh et al., Proc Natl Acad Sci U S A 101:4477-4482, 2004). Additionally, overexpression of Met is associated with enhanced invasiveness of breast cancer cells (Edakuni et al., Pathol Int 51(3):172-178, 2001; Jin et al., Cancer 79(4):749-760, 1997; Tuck et al., Am J Pathol 148(1):225-232, 1996). Here, we review the regulation of recently identified novel downstream mediators of HGF/Met signaling, Breast tumor kinase (Brk/PTK6), and Src-associated substrate during mitosis of 68 kDa (Sam68), and discuss their relevance to mechanisms of breast cancer progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Breast / cytology
  • Breast / metabolism
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Movement
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Disease Progression
  • Female
  • Hepatocyte Growth Factor / metabolism*
  • Humans
  • Mitogen-Activated Protein Kinase 7 / metabolism
  • Neoplasm Proteins / metabolism*
  • Phosphorylation
  • Protein Structure, Tertiary
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-met / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction
  • Tyrosine / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • HGF protein, human
  • KHDRBS1 protein, human
  • Neoplasm Proteins
  • RNA-Binding Proteins
  • Tyrosine
  • Hepatocyte Growth Factor
  • MET protein, human
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-met
  • PTK6 protein, human
  • Mitogen-Activated Protein Kinase 7