EGF stimulates Cdc42-dependent translocation of SCC antigen to the plasma membrane.
Squamous cell carcinoma (SCC) antigen, including intracellular serine protease inhibitors, is widely used as a laboratory marker for cancers of squamous cell origin. Clinical evidences suggest that increased tissue-expression of SCC antigen predicts an invasive phenotype of cancer cells. Herein, we demonstrated that over-expression of SCC antigen increased the rate of EGF-stimulated cell migration. In the search for the underlying molecular mechanism, we have discovered that SCC antigen was translocated to the plasma membrane upon EGF stimulation and co-localized with polymerized-actin at lamellipodia. We further showed that, co-expression of Cdc42, a downstream target of the EGF receptor, enhanced translocation of the SCC antigen, while co-expression of dominant-inhibitory Cdc42 diminished its translocation. These results suggest that EGF-Cdc42 signal regulates the translocation of SCC antigen to the plasma membrane. Lamellipodia at the leading edge might be a site of action of SCC antigen.
Emoto
Tomoko
T
Women's Health Care Unit, Yamaguchi University Hospital, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan. emotosan@yamaguchi-u.ac.jp
Nakamura
Kazuyuki
K
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D019556:COS Cells; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D015843:Serpins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D053778:Thiazolidines / Q000494:pharmacology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D000951:Antigens, Neoplasm; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015843:Serpins; D053778:Thiazolidines; C051072:squamous cell carcinoma-related antigen; D004815:Epidermal Growth Factor; D020764:cdc42 GTP-Binding Protein; C037068:latrunculin B