Anoikis is a programmed cell death that occurs when cells lose their attachment to the extracellular matrix (ECM). Cell adhesion plays an important role in neoplastic transformation. Tumors produce several molecules that facilitate their proliferation, invasion and maintenance, especially proteoglycans. The syndecan-4 (SDC4), a heparan sulfate proteoglycan, can act as a co-receptor of growth factors and proteins of the extracellular matrix (ECM) by increasing the affinity of adhesion molecules to their specific receptors. It participates together with integrins and FAK (focal adhesion kinase) in cell adhesion at focal contacts connecting the ECM to the cytoskeleton. Changes in SDC4 expression have been observed in tumor cells, indicating its involvement in cancer. Our previous works demonstrated that acquisition of anoikis resistance by blocking adhesion to the substrate up-regulates syndecan-4 expression in endothelial cells. So, we decided to further study the specific roles of SDC4 in transformed phenotype of anoikis resistant endothelial cells by specific silencing of SDC4 using micro RNA interference (miR RNAi). Our results indicated that downregulation of SDC4 expression reverses the transformed phenotype of anoikis resistant endothelial cells. A better understanding of the mechanisms underlying anoikis resistance and syndecan-4 expression may provide insight into the biology of cancer and identify novel therapeutic targets for prevention of metastasis formation.
Carla Cristina Lopes, PhD is a Professor of Cell Biology at the Universidade Federal de São Paulo, Brazil. Her major scientific interests are: proteoglycans, cancer, anoikis, metastasis, extracellular matrix and cell signaling. Results of her works are published in prestigious journals, including: Matrix Biology, Apoptosis, International Journal of Biochemistry & Cell Biology, Journal of Colloid and Interface Science, Journal of Cellular Biochemistry, Biochimica et Biophysica Acta, Plos One and others. In addition, she also has four chapters published in the book “Insights into Carbohydrate Structure and Biological Function”.