TGF-beta induces formation of F-actin cores and matrix degradation in human breast cancer cells via distinct signaling pathways.
Transforming growth factor beta regulates many biological processes including cell motility and invasion. Podosomes are specialized F-actin rich structures found in normal cells, such as osteoclasts and macrophages. Tumor cells often form related structures called invadopodia that are thought to promote invasion and metastasis. Here we show that human breast cancer cells organize F-actin rich structures in response to transforming growth factor beta that colocalize with areas of extracellular matrix degradation. We further show that organizing the complex of proteins needed to form these structures requires signaling through phosphatidylinositide 3-kinase and Src kinase, while activating the proteases involved in degradation of extracellular matrix requires extracellular signal-regulated kinase signaling, and that each of these pathways is activated by transforming growth factor beta in CA1D human breast cancer cells.
Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE 68198-7696, USA.
Shyamali
S
Mandal
Keith R
KR
Johnson
Margaret J
MJ
Wheelock
D000199:Actins / Q000378:metabolism*; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000199:Actins; D005780:Gelatin; D020780:Matrix Metalloproteinase 9; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D016212:Transforming Growth Factor beta; D019061:src-Family Kinases