Increased ROS (cellular reactive oxygen species) are characteristic of both fibrosis and tumour development. ROS induce the transdifferentiation to myofibroblasts, the activated form of fibroblasts able to promote cancer progression. Here, we report the role of ROS produced in response to dysfunctions of mitochondrial complex I, in fibroblast activation and in tumour progression. We studied human fibroblasts with mitochondrial dysfunctions of complex I, leading to hyperproduction of ROS. We demonstrated that ROS level produced by the mutated fibroblasts correlates with their activation. The increase of ROS in these cells provides a greater ability to remodel the extracellular matrix leading to an increased motility and invasiveness. Furthermore, we evidentiated that in hypoxic conditions these fibroblasts cause HIF-1α stabilization and promote a proinvasive phenotype of human melanoma cells through secretion of cytokines. These data suggest a possible role of deregulated mitochondrial ROS production in fibrosis evolution as well as in cancer progression and invasion.

Mitochondrial oxidative stress due to complex I dysfunction promotes fibroblast activation and melanoma cell invasiveness / Maria Letizia Taddei, Elisa Giannoni, Giovanni Raugei, Salvatore Scacco, AnnaMaria Sardanelli, Sergio Papa, Paola Chiarugi. - In: JOURNAL OF SIGNAL TRANSDUCTION (ONLINE). - ISSN 2090-1747. - ELETTRONICO. - (2012), pp. 0-0. [10.1155/2012/684592]

Mitochondrial oxidative stress due to complex I dysfunction promotes fibroblast activation and melanoma cell invasiveness

Maria Letizia Taddei;Elisa Giannoni;Giovanni Raugei;Paola Chiarugi
2012

Abstract

Increased ROS (cellular reactive oxygen species) are characteristic of both fibrosis and tumour development. ROS induce the transdifferentiation to myofibroblasts, the activated form of fibroblasts able to promote cancer progression. Here, we report the role of ROS produced in response to dysfunctions of mitochondrial complex I, in fibroblast activation and in tumour progression. We studied human fibroblasts with mitochondrial dysfunctions of complex I, leading to hyperproduction of ROS. We demonstrated that ROS level produced by the mutated fibroblasts correlates with their activation. The increase of ROS in these cells provides a greater ability to remodel the extracellular matrix leading to an increased motility and invasiveness. Furthermore, we evidentiated that in hypoxic conditions these fibroblasts cause HIF-1α stabilization and promote a proinvasive phenotype of human melanoma cells through secretion of cytokines. These data suggest a possible role of deregulated mitochondrial ROS production in fibrosis evolution as well as in cancer progression and invasion.
0
0
Goal 3: Good health and well-being
Maria Letizia Taddei, Elisa Giannoni, Giovanni Raugei, Salvatore Scacco, AnnaMaria Sardanelli, Sergio Papa, Paola Chiarugi
File in questo prodotto:
File Dimensione Formato  
Taddei ML. 2012.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 1.42 MB
Formato Adobe PDF
1.42 MB Adobe PDF Visualizza/Apri

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1282881
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact