title: Caveolin-1-dependent and -independent uPAR signaling pathways contribute to ganglioside GT1b induced early apoptosis in A549 lung cancer cells.
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.
authors.affiliation: Division of Life Science, Korea Basic Science Institute Daejeon 305-333, Korea ; Hyundai Senior High School Seoul 127, Korea.
authors.forename: Jung-Hoo
authors.initials: JH
authors.lastname: Hwang
authors.affiliation: Department of Life Science, Dongguk University Seoul 100-715, Korea.
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Sung
authors.affiliation: NAR Center, Daejeon University Daejeon 301-724, Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Division of Life Science, Korea Basic Science Institute Daejeon 305-333, Korea.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Chung
authors.affiliation: Division of Biological Science and Technology, Yonsei University Wonju 220-100, Korea.
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Park
authors.affiliation: Division of Life Science, Yongin University Yongin 449-714, Korea.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Life Science, Korea Basic Science Institute Daejeon 305-333, Korea.
authors.forename: Ik-Soon
authors.initials: IS
authors.lastname: Jang
keywords: ERK; Lung cancer; caveolin-1; ganglioside GT1b; p53; uPAR