Tobacco smoke activates protein association and tyrosine phosphorylation of the GPI-transamidase complex subunits in human cancers

Yiping Huang, Jatin Nagpal, Barry Trink, Edward Ratovitski

Research output: Contribution to journalReview articlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
JournalJournal of Epithelial Biology and Pharmacology
Volume2
Issue number1
DOIs
StatePublished - 2009

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology

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