Caveolin-1-dependent and -independent uPAR signaling pathways contribute to ganglioside GT1b induced early apoptosis in A549 lung cancer cells

Jung Hoo Hwang, Jung Suk Sung, Jung Min Kim, Young Ho Chung, Jun Soo Park, Seung Hoon Lee, Ik Soon Jang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Urokinase receptor interacts with α5β1-integrin and enhances cancer cell proliferation and metastasis. Activation of α5β1-integrin requires caveolin-1 and is regulated by uPAR, which upregulates persistently the activated ERK necessary for tumor growth. In this study, we show that the ganglioside GT1b induces proapoptotic signaling through two uPAR-ERK signaling pathways in A549 lung cancer cells. GT1b downregulated the expression of α5β1 integrin, caveolin-1, fibronectin, FAK, and ERK, whereas GT1b upregulated the expression of p53 and uPAR, suggesting GT1b mediated depletion of caveolin-1 in uPAR-expressing A549 cells also disrupts uPAR/integrin complexes, resulting in downregulation of fibronectin-α5β1-integrin-ERK signaling. Following p53 siRNA treatment, FAK and ERK expression was recovered, meaning the presence of reentry uPAR-FAK-ERK signaling pathway. These findings reveal that GT1b is involved in both caveolin-1-dependent uPAR-α5β1-integrin-ERK signaling and caveolin-1-independent uPAR-FAK-ERK signaling. These results suggest a novel function of GT1b as a dual regulator of ERK by modulating caveolin-1 and p53.

Original languageEnglish
Pages (from-to)801-810
Number of pages10
JournalAmerican Journal of Cancer Research
Volume4
Issue number6
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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