Transforming growth factor-beta (TGF- β ) is a pleiotropic factor, with several different roles in health and disease. TGF- β has been postulated as a dual factor in tumor progression, since it represses epithelial tumor development in early stages, whereas it stimulates tumor progression in advanced stages. During tumorigenesis, cancer cells acquire the capacity to migrate and invade surrounding tissues and to metastasize different organs. The urokinase-type plasminogen activator (uPA) system, comprising uPA, the uPA cell surface receptor, and plasminogen-plasmin, is involved in the proteolytic degradation of the extracellular matrix and regulates key cellular events by activating intracellular signal pathways, which together allow cancer cells to survive, thus, enhancing cell malignance during tumor progression. Due to their importance, uPA and its receptor are tightly transcriptionally regulated in normal development, but are deregulated in cancer, when their activity and expression are related to further development of cancer. TGF- β regulates uPA expression in cancer cells, while uPA, by plasminogen activation, may activate the secreted latent TGF- β , thus, producing a pernicious cycle which contributes to the enhancement of tumor progression. Here we review the specific roles and the interplay between TGF- β and uPA system in cancer cells and their implication in skin cancer.
Keyphrases
- transforming growth factor
- poor prognosis
- skin cancer
- epithelial mesenchymal transition
- extracellular matrix
- long non coding rna
- papillary thyroid
- cell surface
- healthcare
- public health
- signaling pathway
- binding protein
- squamous cell
- gene expression
- squamous cell carcinoma
- mental health
- transcription factor
- single cell
- young adults
- lymph node metastasis
- risk assessment
- bone marrow
- men who have sex with men