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Comparative proteome analysis reveals flotillin‐1 as a H‐Ras‐interacting lipid raft protein critical for breast epithelial cell invasion
Author(s) -
Moon Aree,
Yong HaeYoung,
Hwang JinSun,
Kim MyeongOk,
Sohn HwaJin,
Kim EunSook,
Choi Wahn Soo,
Kim HyeongReh Choi,
Kim KiBum
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.674.3
Subject(s) - lipid raft , cancer research , biology , microbiology and biotechnology , rac1 , proteome , cell migration , cell , gene knockdown , chemistry , cell culture , signal transduction , bioinformatics , biochemistry , genetics
The objective of the present study was to identify the protein profile specific to the biological processes for breast cell invasion/migration. Complete proteome profiles of lipid raft proteins were provided from three cell lines of differing invasive abilities: non‐invasive MCF10A and N‐Ras MCF10A cells and invasive H‐Ras MCF10A cells. Among 24‐lipid raft proteins which were upregulated in an H‐Ras‐specific manner, we tested whether flotillin‐1 plays a causative role for H‐Ras‐mediated MCF10A cell invasion/migration. Expression of flotillin‐1 was correlated with the pathogenically diagnosed cancer tissues compared to normal tissues, providing the in vivo relevance for the tumorigenic potential of flotillin‐1 in human breast cancer. Importantly, flotillin‐1 colocalizes with H‐Ras in the plasma membrane, but not with N‐Ras. Disruption of lipid raft caused a marked inhibition of H‐Ras activation and invasion/migration, suggesting that the interaction of H‐Ras and flotillin‐1 is critical to the H‐Ras‐induced invasion/migration. Moreover, the knockdown of flotillin‐1 expression reduced the activation of H‐Ras, Rac1 and p38 as well as MMP‐2 and invasive/migratory phenotypes. Taken together, this study identified flotillin‐1 as an H‐Ras‐interacting lipid raft protein critical for the activation of H‐Ras and consequently for the H‐Ras ability to induce invasive potential in breast epithelial cells.