Catenin
Cell-cell adhesion complexes are required for simple epithelia in higher organisms to maintain structure, function and polarity.
These complexes, which help regulate cell growth in addition to creating and maintaining epithelial layers,[6] are known as adherens junctions and they typically include at least cadherin, β-catenin, and α-catenin.
[7] Catenins play roles in cellular organization and polarity long before the development and incorporation of Wnt signaling pathways and cadherins.
[7][8] The primary mechanical role of catenins is to connect cadherins to actin filaments, such as the adhesion junctions of epithelial cells.
First of all, by binding to cadherin receptor intracellular cytoplasmic tail domains,[10] it can act as an integral component of a protein complex in adherens junctions that helps cells maintain epithelial layers.
β-catenin acts by anchoring the actin cytoskeleton to the junctions, and may possibly aid in contact inhibition signaling within the cell.
Following phosphorylation of the N-terminal Ser and Thr residues of β-catenin, BTRC promotes its ubiquitination, which causes it to be degraded by the TrCP/SKP complex.
[11] At this point, β-catenin becomes a coactivator for TCF and LEF to activate Wnt genes by displacing Groucho and HDAC transcription repressors.
[11] While less attention is directed at α-catenin in studies involving cell adhesion, it is nonetheless an important player in cellular organization, function and growth.
Any changes in cytoskeletal organization and adhesion can lead to altered signaling, migration and a loss of contact inhibition that can promote cancer development and tumor formation.
[20][21] In particular, catenins have been identified to be major players in aberrant epithelial cell layer growth associated with various types of cancer.
VEGF-B treatment of hepatoma carcinoma cells can cause α-catenin to move from its normal location on the membrane into the nucleus and E-cadherin expression to decrease, thus promoting EMT and tumor invasiveness.
[33] In the short-term, combining current treatment techniques with therapeutics targeting catenin-associated elements of cancer might be most effective in treating the disease.
By disrupting Wnt/β-catenin signaling pathways, short-term neoadjuvant radiotherapy (STNR) may help prevent clinical recurrence of the disease after surgery, but much more work is needed before an adequate treatment based on this concept can be determined.
One possible way to achieve this, which has been successful in mouse models, is to use inhibitors of Ras activation in order to enhance the functionality of these adhesion systems.
