Journal
ONCOTARGET
Volume 7, Issue 43, Pages 70336-70352Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.11856
Keywords
Focal adhesion kinase; breast cancer; apoptosis; anoikis
Categories
Funding
- Breast Cancer Now
- Cancer Research UK
- Wellcome Trust [088785/Z/09/Z]
- BBSRC CASE PhD studentship
- Astra Zeneca
- Medical Research Council [1343194] Funding Source: researchfish
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A key hallmark of cancer cells is the loss of positional control over growth and survival. Focal adhesion kinase (FAK) is a tyrosine kinase localised at sites of integrinmediated cell adhesion to the extracellular matrix. FAK controls a number of adhesion-dependent cellular functions, including migration, proliferation and survival. Although FAK is overexpressed and activated in metastatic tumours, where it promotes invasion, it can also be elevated in cancers that have yet to become invasive. The contribution of FAK to the early stages of tumourigenesis is not known. We have examined the effect of activating FAK in non-transformed mammary epithelial cells (MECs) to understand its role in tumour initiation. In agreement with previous studies, we find FAK activation in 2D-culture promotes proliferation, migration, and epithelial-to-mesenchymal transition. However in 3D-cultures that better resemble normal tissue morphology, mammary cells largely respond to FAK activation via suppression of apoptosis, promoting aberrant acinar morphogenesis. This is an acquired function of FAK, because endogenous FAK signalling is not required for normal morphogenesis in 3D-culture or in vivo. Thus, FAK activation may facilitate tumour initiation by causing resistance to apoptosis. We suggest that aberrant FAK activation in breast epithelia is dependent upon the tissue context in which it occurs.
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