University of California San Diego, Moores Cancer Center, Department of Reproductive Medicine, 3855 Health Sciences Dr., MC0803, La Jolla, California 92093 USA.
- Florian J. Sulzmaier,
- Christine Jean &
- David D. Schlaepfer
Competing interests statement
The authors declare no competing interests.
Florian J. Sulzmaier
Florian J. Sulzmaier is a postdoctoral fellow at The Moores Cancer Center, University of California, San Diego (UCSD), in La Jolla, California, USA. He completed his Ph.D. at the University of Hawaii at Manoa, studying kinase signalling pathways that control cell metastasis in cancers of the central nervous system. He is currently investigating the role of focal adhesion kinase (FAK) in tumour epithelial-to-mesenchymal transition.
Christine Jean is a postdoctoral fellow at The Moores Cancer Center, University of California, San Diego (UCSD), in La Jolla, California, USA. She completed her Ph.D. at Université de Toulouse, France. Her interests revolve around the role of the microenvironment in modulating tumour growth and metastasis. She is currently investigating mechanisms of endothelial focal adhesion kinase (FAK) signalling on tumour progression.
David D. Schlaepfer
David D. Schlaepfer is a professor in The Moores Cancer Center, University of California, San Diego (UCSD), in La Jolla, California, USA, and has studied focal adhesion kinase (FAK) for more than 20 years. His group uses mouse models to study tumour–stromal interactions, mechanisms of metastasis, preclinical analyses of small molecule FAK inhibitors, and signalling linkages that promote ovarian tumour recurrence and progression.
- Integrin receptor clustering
The formation of multimeric membrane integrin clusters upon binding to extracellular matrix ligands, inducing the formation of multi-protein complexes at cytoplasmic integrin tails to drive focal adhesion formation and cytoskeletal rearrangement.
- Focal adhesions
Multi-protein complexes that regulate cellular attachment by linking the actin cytoskeleton to components of the extracellular matrix via transmembrane receptors termed integrins.
- Epithelial-to-mesenchymal transition
(EMT). A cellular mechanism that allows polarized epithelial cells to acquire a mesenchymal phenotype that is characterized by increased cell migration and invasion and the ability to survive in adhesion-independent conditions.
- Floxed mouse models
Transgenic insertion of loxP sites flanking a gene of interest. Induced expression of Cre recombinase catalyses recombination between the loxP repeats and mediates the deletion of the gene of interest.
- MMTV–PyMT model
A mouse model with conditional expression of the polyomavirus middle T antigen (PyMT) under the control of the mouse mammary tumour virus (MMTV) promoter, inducing the formation of mammary tumours.
- Guanine nucleotide exchange factor
(GEF). A protein that promotes the exchange of GDP for GTP on a GTPase, thereby facilitating its activation.
Specialized membrane protrusions (also known as an invasive pseudopodia) in which active extracellular matrix degradation takes place.
A seven-subunit protein complex that is involved in regulation of the actin cytoskeleton; it mediates the nucleation of branched actin filaments.
- Neural Wiskott–Aldrich syndrome protein
(N-WASP). A protein that promotes actin polymerization by stimulating the activity of the ARP2/3 complex.
Cell death (apoptosis) that is induced by the loss of cell matrix adhesion and a physiological mechanism to prevent cell displacement.
A collection of cells arising from a single cell of mammary origin through clonal growth in culture.
- Vascular normalization
The process of restoring normal vasculature from the classical cancer-associated tortuous and leaky vessels. This phenomenon involves increased vascular pericyte coverage and decreased vascular permeability and hypoxia, and it results in decreased metastasis and increased blood perfusion, rendering vessels more efficient for oxygen and drug delivery.
- Tumour cell extravasation
The crucial step in tumour metastasis in which tumour cells exit the vasculature to penetrate target organs. This requires tumour cell adhesion to the endothelium, spreading out across endothelial cells, and penetration of the basement membrane.
- ATP site hinge
A segment that connects the two lobes of a kinase domain. Hinge and kinase lobes form an interface that creates the ATP-binding pocket.