Cobalt chloride stimulates phosphoinositide 3-kinase/Akt signaling through the epidermal growth factor receptor in oral squamous cell carcinoma.
Tumor cells are often found under hypoxic conditions due to the rapid outgrowth of their vascular supply, and, in order to survive hypoxia, these cells induce numerous signaling factors. Akt is an important kinase in cell survival, and its activity is regulated by the upstream phosphoinositide 3-kinase (PI3K) and receptor tyrosine kinases (RTKs). In this study, we examined Akt activation and RTKs/PI3K/Akt signaling using the hypoxia-mimetic cobalt chloride in oral squamous carcinoma cells. Cobalt chloride increases Akt phosphorylation in both a dose- and time-dependent manner. Blocking the activation of the PI3K/Akt pathway using LY294002 abolished Akt activation in response to cobalt chloride, suggesting that Akt phosphorylation by cobalt chloride is dependent on PI3K. In addition, activation of the PI3K/Akt pathway seems to rely on the epidermal growth factor receptor (EGFR), since the inhibition of EGFR attenuated cobalt chloride-induced Akt activation. The results in this study also demonstrate that cobalt chloride increases EGFR protein levels and induces oral squamous cell carcinoma cells to enter S phase.
Ryu
Mi Heon
MH
Department of Oral Pathology, School of Dentistry, Pusan National University, Beomeo-ri, Mulgeum-Eup, Yangsan 626-870, South Korea.
Park
Jeong Hee
JH
Park
Ji Eun
JE
Chung
Jin
J
Lee
Chang Hun
CH
Park
Hae Ryoun
HR
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000187:drug effects; D045744:Cell Line, Tumor; D003035:Cobalt / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D004273:DNA, Neoplasm; D003035:Cobalt; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; C018021:cobaltous chloride