Integrin-linked kinase (ILK) and estrogen receptor (ER)-A modulate cell migration. However, the crosstalk between ERA and ILK and the role ofILK in ERA-mediated cell migration remain unexplored. Here, we report that ILK participates in ERA signaling in breast cancer cells. We found that ILK binds ERA in vitro and in vivo through a LXXLL motifin ILK. Estrogen prevented ERA-ILK binding, resulting in phosphatidylinositol 3-kinase (PI3K)–dependent increase in ILK kinase activity. Furthermore, the regulation ofER A-ILK interaction was dependent on the PI3K pathway. Unexpectedly, transient knockdown or inhibition ofILK caused hyperphosphorylation ofER A 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. (Cancer Res 2006;66(22): 11030-8)

Acconcia, F., Manavathi, B., Mascarenhas, J., Talukder, A.h., Mills, G., Kumar, R. (2006). An inherent role of integrin-linked kinase-estrogen receptor alpha interaction in cell migration. CANCER RESEARCH, 66, 11030-11038 [10.1158/0008-5472.CAN-06-2676].

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

ACCONCIA, FILIPPO;
2006

Abstract

Integrin-linked kinase (ILK) and estrogen receptor (ER)-A modulate cell migration. However, the crosstalk between ERA and ILK and the role ofILK in ERA-mediated cell migration remain unexplored. Here, we report that ILK participates in ERA signaling in breast cancer cells. We found that ILK binds ERA in vitro and in vivo through a LXXLL motifin ILK. Estrogen prevented ERA-ILK binding, resulting in phosphatidylinositol 3-kinase (PI3K)–dependent increase in ILK kinase activity. Furthermore, the regulation ofER A-ILK interaction was dependent on the PI3K pathway. Unexpectedly, transient knockdown or inhibition ofILK caused hyperphosphorylation ofER A 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. (Cancer Res 2006;66(22): 11030-8)
Acconcia, F., Manavathi, B., Mascarenhas, J., Talukder, A.h., Mills, G., Kumar, R. (2006). An inherent role of integrin-linked kinase-estrogen receptor alpha interaction in cell migration. CANCER RESEARCH, 66, 11030-11038 [10.1158/0008-5472.CAN-06-2676].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11590/148490
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