Pressure stimulates breast cancer cell adhesion independently of cell cycle and apoptosis regulatory protein (CARP)-1 regulation of focal adhesion kinase.
BACKGROUND
Pressure stimulates colon cancer adhesion via focal adhesion kinase (FAK). Extracellular pressures reaching 29 mm Hg have been reported in rapidly growing breast cancers, and tumors experience pressure during surgical manipulation. We hypothesized that pressure stimulates breast cancer adhesion and that CARP-1, which influences cancer biology, inhibits FAK, and modulates pressure effects.


METHODS
We compared MDA-MB-468 breast cancer cells under ambient or 15-mm Hg increased pressure. We studied FAK-397 autophosphorylation, which parallels activation, after CARP-1 overexpression, and investigated whether CARP-1 stable overexpression or reduction alters pressure-stimulated adhesion.


RESULTS
Pressure increased MDA-MB-468 adhesion 25% (n = 30, P < .05). CARP-1 overexpression inhibited FAK-397 phosphorylation. However, pressure stimulated adhesion equivalently in CARP-1-overexpressing and CARP-1-reduced lines (n = 6, P < .05).


CONCLUSIONS
Pressure within proliferative tumors or during manipulation may activate breast cancer cells. Thus, inhibiting pressure signaling in rapidly growing breast tumors may be beneficial. CARP-1 does regulate FAK, but CARP-1 modulation does not alter pressure-stimulated adhesion. Targeting CARP-1 is unlikely to manipulate this pathway.
Downey
Christina
C
Department of Surgery, John D. Dingell VA Medical Center, Wayne State University, 4646 John R Street, Detroit, MI 48201-1932, USA.
Alwan
Kamal
K
Thamilselvan
Vijayalakshmi
V
Zhang
Liyue
L
Jiang
Yan
Y
Rishi
Arun K
AK
Basson
Marc D
MD
D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000503:physiopathology*; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D051417:Focal Adhesion Kinase 1 / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D011312:Pressure; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C477529:CCAR1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human