Cancer cells are exposed to a wide range of stress sources, such as nutrient deprivation and hypoxia, as well as cytotoxic chemotherapy and radiotherapy. Certain forms of stress can also promote survival activating the metabolic autophagy pathway in cancer cells. Autophagy is dramatically increased in cancer cells. In these conditions, it is becoming evident that autophagy protects cells, by providing an alternative energy source and by eliminating dysfunctional organelles or proteins. Its role in tumorigenesis is more controversial and both the presence and the absence of autophagy have been implicated. Autophagy is known to be associated with the poor outcome of patients with various types of cancers, and its effectiveness as a prognostic marker in colorectal cancer was demonstrated by several studies. The inhibition of autophagy may be a potential therapeutic target in colorectal cancer. In vitro experiments have shown that the inhibition of autophagy increases 5-FU-induced apoptosis. There are two trials currently investigating the addition of chloroquine to 5-FU-based chemotherapy and bevacizumab. In the present study, we evaluated the expression of LC3B-II in samples of human colorectal microadenomas (i.e., dysplastic aberrant crypt foci) and carcinomas compared to normal mucosa. Furthermore, the expression pattern of LC3B-II was assessed in carcinomas classified as DNA microsatellite stable (MSS) and unstable (MSI). Thus, immunofluorescence techniques coupled with confocal microscopy and immunoblot experiments were performed. The results clearly showed a significant increase in expression of the autophagic key factor in microadenomas and carcinomas with respect to normal mucosa. In MSS carcinomas, the level of LC3B-II expression was higher than that in the MSI carcinomas.
|Data di pubblicazione:||2015|
|Titolo:||Autophagy is upregulated during colorectal carcinogenesis, and in DNA microsatellite stable carcinomas|
|Autore/i:||Sena, Paola; Mariani, Francesco; Mancini, Stefano; Benincasa, Marta; Magnani, Giulia; Pedroni, Monica; Palumbo, Carla; Roncucci, Luca|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3892/or.2015.4326|
|Codice identificativo ISI:||WOS:000364617000047|
|Codice identificativo Scopus:||2-s2.0-84943789057|
|Codice identificativo Pubmed:||26502823|
|Citazione:||Autophagy is upregulated during colorectal carcinogenesis, and in DNA microsatellite stable carcinomas / Sena, Paola; Mariani, Francesco; Mancini, Stefano; Benincasa, Marta; Magnani, Giulia; Pedroni, Monica; Palumbo, Carla; Roncucci, Luca. - In: ONCOLOGY REPORTS. - ISSN 1021-335X. - 34(2015), pp. 3222-3230.|
|Tipologia||Articolo su rivista|
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