Table III.
Targeting molecular mechanisms that support cell-cell interactions.
| Target | Molecular Mechanism | Reference |
|---|---|---|
| E-Cadherin | Cell-Cell adhesion molecule of the cadherin family involved in the regulation of epithelial cell-cell adhesion. Routinely mislocalized or lost in patients with metastatic disease. Experimental over expression can inhibit migration while knock down or cellular relocalization in response to pro-migratory cytokines can promote motility and migration. Generally considered a negative regulator of cell motility. | [40, 118, 176] |
| N-Cadherin | Cell-Cell adhesion molecule of the cadherin family involved in the regulation of epithelial cell-cell adhesion. Expressed during epithelial-mesenchymal transition and upregulated in metastatic disease. Upregulation frequently coincides with the loss of E-Cadherin. Association with FGFR-1 enhances receptor signaling and provides a prometastatic mechanism of motility | [117–119][120] |
| EpCam | Cell-Cell adhesion molecule of the immunoglobulin super family. Can function as a tumor suppressor or oncogene because it inhibit motility but also abrograte E-cadherin mediated adhesion to promote tumor cell motility. | [120, 121] |
| ALCAM | Cell-Cell adhesion molecule of the immunogobulin super family. Can inhibit motility when engaged in cell-cell interactions or promote motility when cleaved by ADAM17. Expression is upregulated in prostate, pancreatic, and colorectal cancer but down regulated in breast cancer. Shedding is elevated in all cancers and the shed ectodomain is being explored as a biomarker of metastasis. | [75, 174, 175] |
| Claudin 1, 4, and 7 | Cell-Cell adhesion molecule of the Claudin family involved in transmitting cell-cell contact to the actin cytoskeleton within the tight junction. Loss of Claudins enhances motility and metastasis. | [95, 122–124] |
| EphA2 | Cell-Cell adhesion molecule of the ephrin family capable of promoting motility and metastasis. Integrates with Src, Akt, and HGF-mediated signaling. | [74, 173] |
Molecules included here are representative molecular determinants of the underlying principle