Metastasis: tumor cells becoming MENAcing.
During breast cancer metastasis cells emigrate from the primary tumor to the bloodstream, and this carries them to distant sites where they infiltrate and sometimes form metastases within target organs. These cells must penetrate the dense extracellular matrix comprising the basement membrane of the mammary duct/acinus and migrate toward blood and lymphatic vessels, processes that mammary tumor cells execute primarily using epidermal growth factor (EGF)-dependent protrusive and migratory activity. Here, we focus on how the actin regulatory protein Mena affects EGF-elicited movement, invasion and metastasis. Recent findings indicate that, in invasive migratory tumor cells, Mena isoforms that endow heightened sensitivity to EGF and increased protrusive and migratory abilities are upregulated, whereas other isoforms are selectively downregulated. This change in Mena isoform expression enables tumor cells to invade in response to otherwise benign EGF stimulus levels and could offer an opportunity to identify metastatic risk in patients.
Department of Biology and Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology (MIT), 77 Massachusetts Ave, Cambridge, MA 02138, USA. fgertler@MIT.EDU
Frank
F
Gertler
John
J
Condeelis
D000199:Actins / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D020869:Gene Expression Profiling; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D009362:Neoplasm Metastasis; D059016:Tumor Microenvironment
D000199:Actins; C511939:Enah protein, human; D008840:Microfilament Proteins