TY - JOUR
T1 - Alpha6beta4 integrin crosslinking induces EGFR clustering and promotes EGF-mediated Rho activation in breast cancer
AU - Gilcrease, Michael Z.
AU - Zhou, Xiao
AU - Lu, Xiaolin
AU - Woodward, Wendy A.
AU - Hall, Brian E.
AU - Morrissey, Phillip J.
N1 - Funding Information:
This work was supported by a grant from the Susan G. Komen Breast Cancer Foundation (BCTR022043) and a developmental award from The University of Texas M.D. Anderson SPORE in Breast Cancer (NIH 5P50CA116199-02) to MZG and by Cancer Center Support Grant # CA16672 from the NCI.
PY - 2009
Y1 - 2009
N2 - Background. The 64 integrin is overexpressed in the basal subtype of breast cancer and plays an important role in tumor cell motility and invasion. EGFR is also overexpressed in the basal subtype of breast cancer, and crosstalk between 64 integrin and EGFR appears to be important in tumor progression. Methods. We evaluated the effects of 64 crosslinking on the distribution and function of EGFR in breast carcinoma cell line MDA-MB-231. Receptor distribution was evaluated by fluorescence microscopy and multispectral imaging flow cytometry, and ligand-mediated EGFR signaling was evaluated using Western blots and a Rho pull-down assay. Results. Antibody-mediated crosslinking of 64 integrin was sufficient to induce cell-surface clustering of not only 64 but also EGFR in nonadherent cells. The induced clustering of EGFR was observed minimally after 5 min of integrin crosslinking but was more prominent after 15 min. EGFR clustering had minimal effect on the phosphorylation of Akt or Erk1,2 in response to EGF in suspended cells or in response to HB-EGF in adherent cells. However, EGFR clustering induced by crosslinking 64 had a marked effect on Rho activation in response to EGF. Conclusion. Crosslinking 64 integrin in breast carcinoma cells induces EGFR clustering and preferentially promotes Rho activation in response to EGF. We hypothesize that this integrin-EGFR crosstalk may facilitate tumor cell cytoskeletal rearrangements important for tumor progression.
AB - Background. The 64 integrin is overexpressed in the basal subtype of breast cancer and plays an important role in tumor cell motility and invasion. EGFR is also overexpressed in the basal subtype of breast cancer, and crosstalk between 64 integrin and EGFR appears to be important in tumor progression. Methods. We evaluated the effects of 64 crosslinking on the distribution and function of EGFR in breast carcinoma cell line MDA-MB-231. Receptor distribution was evaluated by fluorescence microscopy and multispectral imaging flow cytometry, and ligand-mediated EGFR signaling was evaluated using Western blots and a Rho pull-down assay. Results. Antibody-mediated crosslinking of 64 integrin was sufficient to induce cell-surface clustering of not only 64 but also EGFR in nonadherent cells. The induced clustering of EGFR was observed minimally after 5 min of integrin crosslinking but was more prominent after 15 min. EGFR clustering had minimal effect on the phosphorylation of Akt or Erk1,2 in response to EGF in suspended cells or in response to HB-EGF in adherent cells. However, EGFR clustering induced by crosslinking 64 had a marked effect on Rho activation in response to EGF. Conclusion. Crosslinking 64 integrin in breast carcinoma cells induces EGFR clustering and preferentially promotes Rho activation in response to EGF. We hypothesize that this integrin-EGFR crosstalk may facilitate tumor cell cytoskeletal rearrangements important for tumor progression.
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U2 - 10.1186/1756-9966-28-67
DO - 10.1186/1756-9966-28-67
M3 - Article
C2 - 19470173
AN - SCOPUS:67949097338
SN - 0392-9078
VL - 28
JO - Journal of Experimental and Clinical Cancer Research
JF - Journal of Experimental and Clinical Cancer Research
IS - 1
M1 - 67
ER -