Table V.

Targeting mechanisms that support molecular integration.

Target	Molecular Mechanism	Reference
CD151	Transmembrane scaffolding protein of the Tetraspanin Super Family. CD151 interacts with other tertraspanins as wel as unique partners including integrins α3β1 and α6β1, MMP14, MMP7, PKC, PI4K and other. These tetraspanin-partner dimers are incorporated into macromolecular complexes known as tetraspanin-enriched microdomains through the homo- and hetero-dimerization of the tetraspanins.	[98, 99, 169]
Talin-1	Integrin adaptor protein that binds to the cytoplasmic tail of the β subunit tail and links the integrin to the actin cytoskeleton and complexes Vinculin and FAK into a functional complex that controls inside-out activation of the integrin and outside-in signaling resulting from matrix binding. Silencing Talin reduces metastasis	[154–156]
FAK	Non-receptor tyrosine kinase that binds to Focal Adhesion Complexes by binding Talin and Paxillin. It interacts with a wide variety of signaling molecules including src, PI3K, Shc, PLCγ, P130Cas, RhoGEF, GRB2, and more. Phosphorylation of its partners by FAK regulates motility.	[165–168]
P120 Catenin	Intracellular scaffolding protein of the catenin family that stabilizes the formation of E-Cadherin based adhesions and integrates cadherin, src, and RTK signaling through scafolding of intracellular signaling molecules. P120 is frequently lost or mutated in cancer thereby disrupting the function of E-cadherin and other, currently undefined, signaling components.	[87, 88, 157]
Cortactin	Actin binding protein that also binds to WASP, MIM, Hax-1, TEM7, Dynamin 2, CD2AP, and Cadherins. Cortactin seems to be important for invasive activity associated with invadapodia present in invasive cells. Cortactin is strongly correlated with cancer progression although its specific role remains unclear.	[162–164]
SPARC	Matricellular protein capable of interacting with collagen, fibronectin, EGF, TGFβ, and the β1 integrin. It alters the composition, assembly, and maturation of ECM. SPARC is upregulated in a large number of cancers although its biological contribution to metastasis is very context dependent.	[158, 159]
P130 CAS	Intracellular scaffolding protein defined as an integrin adaptor molecule. P130cas is capable of binding a very broad range of cytoplasmic signaling molecules including FAK, PYK2, FRNK, PTPNI2, RAPGEF1, CRK, NCK, SFK, Aurora A, and PI3K. It is participates in both transformation and migration.	[91, 160, 161]

Molecules included here are representative molecular determinants of the underlying principle