An inherent role of integrin-linked kinase-estrogen receptor α interaction in cell migration

Filippo Acconcia, Bramanandam Manavathi, Joseph Mascarenhas, Amjad H. Talukder, Gordon Mills, Rakesh Kumar

    Research output: Contribution to journalArticle

    32 Scopus citations


    Integrin-linked kinase (ILK) and estrogen receptor (ER)-α modulate cell migration. However, the crosstalk between ERα and ILK and the role of ILK in ERα-mediated cell migration remain unexplored. Here, we report that ILK participates in ERα signaling in breast cancer cells. We found that ILK binds ERα in vitro and in vivo through a LXXLL motif in ILK. Estrogen prevented ERα-ILK binding, resulting in phosphatidylinositol 3-kinase (PI3K)-dependent increase in ILK kinase activity. Furthermore, the regulation of ERα-ILK interaction was dependent on the PI3K pathway. Unexpectedly, transient knockdown or inhibition of ILK caused hyperphosphorylation of ERα Ser118 in an extracellular signal-regulated kinase/ mitogen-activated protein kinase pathway-dependent manner and an enhanced ERa recruitment to the target chromatin and gene expression, a process reversed by overexpression of ILK. Compatible with these interactions, estrogen regulated cell migration via the PI3K/ILK/AKT pathway with stable ILK overexpression hyperactivating cell migration. Thus, status of ILK signaling may be an important modifier of ER signaling in breast cancer cells and this pathway could be exploited for therapeutic intervention in breast cancer cells.

    Original languageEnglish (US)
    Pages (from-to)11030-11038
    Number of pages9
    JournalCancer Research
    Issue number22
    StatePublished - Nov 15 2006

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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