IGF-IR cooperates with ERα to inhibit breast cancer cell aggressiveness by regulating the expression and localisation of ECM molecules
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
IGF-IR cooperates with ERα to inhibit breast cancer cell aggressiveness by regulating the expression and localisation of ECM molecules. / Afratis, Nikolaos A; Bouris, Panagiotis; Skandalis, Spyros S; Multhaupt, Hinke A; Couchman, John R; Theocharis, Achilleas D; Karamanos, Nikos K.
In: Scientific Reports, Vol. 7, 40138, 2017.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - IGF-IR cooperates with ERα to inhibit breast cancer cell aggressiveness by regulating the expression and localisation of ECM molecules
AU - Afratis, Nikolaos A
AU - Bouris, Panagiotis
AU - Skandalis, Spyros S
AU - Multhaupt, Hinke A
AU - Couchman, John R
AU - Theocharis, Achilleas D
AU - Karamanos, Nikos K
PY - 2017
Y1 - 2017
N2 - IGF-IR is highly associated with the behaviour of breast cancer cells. In ERα-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERα-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules. In particular, activation of IGF-IR, but not EGFR, in MCF-7 breast cancer cells results in the reduction of specific matrix metalloproteinases and their inhibitors. In contrast, IGF-IR inhibition leads to the depletion by endocytosis of syndecan-4. Global important changes in cell adhesion receptors, which include integrins and syndecan-4 triggered by IGF-IR inhibition, regulate adhesion and invasion. Cell function assays that were performed in MCF-7 cells as well as their ERα-suppressed counterparts indicate that ER status is a major determinant of IGF-IR regulatory role on cell adhesion and invasion. The strong inhibitory role of IGF-IR on breast cancer cells aggressiveness for which E2-ERα signaling pathway seems to be essential, highlights IGF-IR as a major molecular target for novel therapeutic strategies.
AB - IGF-IR is highly associated with the behaviour of breast cancer cells. In ERα-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERα-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules. In particular, activation of IGF-IR, but not EGFR, in MCF-7 breast cancer cells results in the reduction of specific matrix metalloproteinases and their inhibitors. In contrast, IGF-IR inhibition leads to the depletion by endocytosis of syndecan-4. Global important changes in cell adhesion receptors, which include integrins and syndecan-4 triggered by IGF-IR inhibition, regulate adhesion and invasion. Cell function assays that were performed in MCF-7 cells as well as their ERα-suppressed counterparts indicate that ER status is a major determinant of IGF-IR regulatory role on cell adhesion and invasion. The strong inhibitory role of IGF-IR on breast cancer cells aggressiveness for which E2-ERα signaling pathway seems to be essential, highlights IGF-IR as a major molecular target for novel therapeutic strategies.
U2 - 10.1038/srep40138
DO - 10.1038/srep40138
M3 - Journal article
C2 - 28079144
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 40138
ER -
ID: 172330932