Vias de señalizacion que regulan la expreslon de proteasas durante la progresion tumoral

Translated title of the contribution: Signaling pathways regulating the expression of proteases during tumor progression

Elisa Bal De Kier Joffé, Esteban Mazzoni, Julio A. Aguirre Ghiso

Research output: Contribution to journalArticle

Abstract

Deregulation of several signaling pathways have been found to be critical for the development of different types of tumors, both in transgenic and spontaneous models. The role of proteases and adhesion molecules during the early stages of tumor progression induced by oncogenes in epithelial and mesenchymal tumors has remained relatively unexplored. This review summarizes recent work showing that different but overlapping signaling effector modules (PKC, v-Ras-RalA-PLD1 or v-Src-RalA-PLD1) induce changes in the production of proteases (uPA and MMPs) and adhesion molecules (fibronectin, CD44, β1-integrin) in normal epithelial or mesenchymal cell lines, associated with tumor development in vivo. Overexpression of PKCγ in normal mammary epithelial cells or of v-Src and v-Ras in NIH3T3 fibroblasts induced in all cases overproduction of uPA and MMPs and a tumorigenic phenotype. Proteases production and tumorigenicity in transformed NIH3T3 cells were dependent on the GTPase RalA. In contrast to the common outcome in protease production by the different tumor promoting stimuli, fibronectin production was high in PKC-overexpressing mammary epithelial cells and it was organized into a rich fibrillar matrix, while oncogene transformed fibroblasts displayed reduced fibronectin production and a total loss of FN fibrillogenesis, an effect also dependent on RalA. These results show that protease overexpression is a common denominator in the acquisition of a malignant phenotype both in mesenchymal and epithelial cells. In contrast there is a dramatic difference in the expression and function of adhesion molecules like fibronectin between these two cell types, suggesting different regulatory roles for this glycoprotein during tumor progression, in cells of different tissular origin.

Original languageSpanish
Pages (from-to)34-40
Number of pages7
JournalMedicina
Volume60
Issue numberSUPPL. 2
StatePublished - Dec 1 2000

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Keywords

  • Fibronectin
  • Invasion and metastases
  • Oncogenes
  • PKC
  • PLD
  • Proteases
  • RalA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bal De Kier Joffé, E., Mazzoni, E., & Aguirre Ghiso, J. A. (2000). Vias de señalizacion que regulan la expreslon de proteasas durante la progresion tumoral. Medicina, 60(SUPPL. 2), 34-40.