TY - JOUR
T1 - Tobacco smoke activates protein association and tyrosine phosphorylation of the GPI-transamidase complex subunits in human cancers
AU - Huang, Yiping
AU - Nagpal, Jatin
AU - Trink, Barry
AU - Ratovitski, Edward
PY - 2009
Y1 - 2009
N2 - We previously found that the protein subunits of GPI-transamidase complex (e.g. PIG-U, PIG-T and GPAA1) play critical roles of oncogenes in human bladder and breast cancers manifesting their activities through signaling mechanisms that involve urokinase receptor/Stat3 and paxillin pathways. We report here that cigarette smoke extract (CSE) enhanced colony formation and invasiveness of certain human cancer cells (e.g. head and neck, bladder or breast). We found that CSE induced the complex formation between PIG-U, PIG-T and GPAA1 proteins and also the association between GPAA1 and EGFR in cancer cells. We observed that inhibitors of EGFR tyrosine kinase, Gefitinib or Erlotinib, modulated tyrosine phosphorylation of PIG-U and PIG-T induced by CSE. We also found that EGFR tyrosine kinase inhibitors and siRNA silencing of PIG-U, PIG-T or GPAA1 modulated the CSE-induced increase in colony formation and invasiveness of human bladder cancer cells. We suggest that the novel mechanism overlapping the oncogenic potential of PIG-U, PIG-T and GPAA1 implicates EGFR tyrosine phosphorylation of PIG-U or PIG-T and subsequent paxillin phosphorylation.
AB - We previously found that the protein subunits of GPI-transamidase complex (e.g. PIG-U, PIG-T and GPAA1) play critical roles of oncogenes in human bladder and breast cancers manifesting their activities through signaling mechanisms that involve urokinase receptor/Stat3 and paxillin pathways. We report here that cigarette smoke extract (CSE) enhanced colony formation and invasiveness of certain human cancer cells (e.g. head and neck, bladder or breast). We found that CSE induced the complex formation between PIG-U, PIG-T and GPAA1 proteins and also the association between GPAA1 and EGFR in cancer cells. We observed that inhibitors of EGFR tyrosine kinase, Gefitinib or Erlotinib, modulated tyrosine phosphorylation of PIG-U and PIG-T induced by CSE. We also found that EGFR tyrosine kinase inhibitors and siRNA silencing of PIG-U, PIG-T or GPAA1 modulated the CSE-induced increase in colony formation and invasiveness of human bladder cancer cells. We suggest that the novel mechanism overlapping the oncogenic potential of PIG-U, PIG-T and GPAA1 implicates EGFR tyrosine phosphorylation of PIG-U or PIG-T and subsequent paxillin phosphorylation.
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U2 - 10.2174/1875044300902010014
DO - 10.2174/1875044300902010014
M3 - Review article
AN - SCOPUS:77953416804
SN - 1875-0443
VL - 2
SP - 14
EP - 22
JO - Journal of Epithelial Biology and Pharmacology
JF - Journal of Epithelial Biology and Pharmacology
IS - 1
ER -