|Questions of A More Technical Nature|
Cadherins: Sticking Together and Sorting Things Out
Cadherins and tissue formation: integrating adhesion and signaling.
Bioessays 1999 Mar;21(3):211-20
Vleminckx K, Kemler R.
Cadherins and other cell-substrate and cell-cell adhesion molecules play an essential role during development. Through their cytoplasmic interaction with the cytoskeleton, cell adhesion molecules physically link cells with the extracellular matrix and/or with each other. These interactions create architectural and structural entities that enable the tissues in the embryo to restrain the physical forces encountered during development. Regulated cell adhesion is also often the driving force of morphogenetic movements. This review goes beyond the adhesive aspect of cadherins, focusing on their roles as signaling molecules in development. We discuss how cadherins, through their effects on cell proliferation, cell death, cell polarization, and differentiation, play a role in the formation of tissues and organs in the developing embryo.
Cadherins are a class of adhesion molecules, typically part of the 'tight junction' that hold cells together. These tight junctions also tend to keep cells from misbehaving, due to the phenomena of 'contact inhibition.' Thus it is logical for defects in cancer cells, such as the ability to metastasize, to be linked with defects in cadherin synthesis. One cadherin in particular, E-cadherin, is associated with the development of metastasis in sevral common cancers, including prostate (1), breast(2) and stomach(3). Since it has been speculated that metastasis of cancer cells through the blood stream is inherrently hostile, and that fewer than 10,000 cancer cells may be involved in the initial metastatic event, development of strategies to re-establish cadherin integrity are on the forefront of medical research.
1.Arenas MI, Romo E, Royuela M, Fraile B, Paniagua R. E-, N- and P-cadherin, and alpha-, beta- and gamma-catenin protein expression in normal, hyperplastic and carcinomatous human prostate. Histochem J. 2000 Nov;32(11):659-67.
2.Madhavan M, Srinivas P, Abraham E, Ahmed I, Mathew A, Vijayalekshmi NR, Balaram P. Cadherins as predictive markers of nodal metastasis in breast cancer. Mod Pathol. 2001 May;14(5):423-7
3.Chan AO, Lam SK, Chu KM, Lam CM, Kwok E, Leung SY, Yuen ST, Law SY, Hui WM, Lai KC, Wong CY, Hu HC, Lai CL, Wong J. Soluble E-cadherin is a valid prognostic marker in gastric carcinoma. Gut. 2001 Jun;48(6):808-11.