Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions

Miracco, Clelia; Cevenini, Gabriele; Franchi, Alessandro; Luzi, Pietro; Cosci, Elena; Mourmouras, Vasileios; Monciatti, Irene; Mannucci, Susanna; Biagioli, Maurizio; Toscano, Marzia; Moretti, Daniele; Lio, Roberto; Massi, Daniela

doi:10.1016/j.humpath.2009.09.004

Cited by 132 publications

(119 citation statements)

References 42 publications

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“…It should be mentioned, however, that a substantial proportion of cases amounting to 31% in our material, also showed a distinct perinuclear MAP1LC3A expression. This is not entirely unexpected, since an analogous 'paranuclear pinpoint stain' was described by Miracco et al 38 in their series of cutaneous malignant melanomas. Rieber and Rieber 37 investigating human C8161 melanoma cells, also noted that 30% of UV-irradiated melanomas showed this juxta-or perinuclear pattern of expression.…”

Section: Discussionsupporting

confidence: 64%

“…With regard to BECN1, an autophagy-related gene with tumor suppressor activity, Miracco et al 38 reported comparable results to those shown for MAP1LC3A, that is gradual decline of cytoplasmic expression of BECN1 in cutaneous melanocytic lesions from 100% in benign nevi to 86.4% in dysplastic nevi, 54.3% in melanomas, and 26.7% in melanoma metastases. Such decreased cytoplasmic expression of BECN1 has been correlated with tumor progression in breast, ovarian, and cerebral neoplasms 39,46,47 and with a reduced survival rate in neoplasms of esophageal, colorectal, hepatocellular, and cerebral origin.…”

Section: Discussionmentioning

confidence: 69%

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Autophagy patterns and prognosis in uveal melanomas

et al. 2011

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Autophagy is a self-degradation mechanism by which cells recycle their own cytoplasmic constituents. It has been claimed that, under certain conditions, such a process may be associated with tumor progression. In this study, the autophagic activity was investigated in a series of 99 uveal melanomas after immunohistochemical staining for the autophagy-associated proteins MAP1LC3A and BECN1, most commonly known as LC3A and Beclin 1, respectively. These were assessed in parallel with the hypoxia-inducible factor 1a (HIF1A) and its downstream protein lactate dehydrogenase 5 (composed by five LDHA subunits). Increased autophagic reactivity, detected by MAP1LC3A or BECN1, was associated with intense pigmentation and tumor hypoxia. Uveal melanomas with extensive overexpression of BECN1 or those with underexpression of this protein were associated with the worst prognosis, but the former manifested metastases much earlier than the latter; only 58% of patients with extensive BECN1 overexpression were alive at 4 years, compared with 80% of patients with underexpressed patterns. It is concluded that autophagy is commonly upregulated in uveal melanomas, and may be associated with hypoxia and intense pigmentation. There is a strong association between extensive BECN1 overexpression and early metastases/poor prognosis, and between underexpression of this protein and late metastases/better prognosis.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 69%

Autophagy patterns and prognosis in uveal melanomas

et al. 2011

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“…Expression of Beclin 1 is low in melanoma and the decrease in Beclin 1 levels was shown to correlate with melanoma progression 21 . Conversely, Mcl-1 has been associated with melanoma progression 28 and shown to be critical for survival of melanoma cells undergoing ER stress 29 or anoikis 30 .…”

Section: Resultsmentioning

confidence: 99%

“…Beclin 1 is a haplo-insufficient tumour suppressor that is frequently deleted or downregulated in several types of tumours [18][19][20][21] . Enhanced expression of Beclin 1 is associated with inhibition of cellular proliferation and diminished in vitro clonogenic survival 11 and xenograft tumour growth 19 .…”

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confidence: 99%

Beclin 1 restrains tumorigenesis through Mcl-1 destabilization in an autophagy-independent reciprocal manner

et al. 2014

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“…Importantly, some of these abnormalities have been shown to correlate with clinicopathological parameters and disease outcomes including overall survival in cancer patients. These findings not only underscore a pivotal role of autophagy in tumorigenesis, but also highlight the possibility of using autophagy-associated molecules as novel prognostic markers in clinical settings (Russell et al, 1990;Eccles et al, 1992;Futreal et al, 1992;Cliby et al, 1993;Saito et al, 1993;Gao et al, 1995;Ahn et al, 2007;Miracco et al, 2007Miracco et al, , 2010Ding et al, 2008;Fujii et al, 2008;Yoshioka et al, 2008;Kim et al, 2008a;Kang et al, 2009;Lazova and Pawelek, 2009;Nomura et al, 2009;Othman et al, 2009;Pirtoli et al, 2009;Li et al, 2009Zhang et al, 2009a;Koukourakis et al, 2010;Lazova et al, 2010;Miao et al, 2010;Negri et al, 2010;Sivridis et al, 2010;Wan et al, 2010;Karpathiou et al, 2010;Chang et al, 2011;Ma et al, 2011).…”

Section: Dysregulation Of Autophagy In Human Cancersmentioning

confidence: 89%

The autophagic paradox in cancer therapy

et al. 2011

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Autophagy, hallmarked by the formation of doublemembrane bound organelles known as autophagosomes, is a lysosome-dependent pathway for protein degradation. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in earlystage carcinogenesis, autophagy inhibits inflammation and promotes genomic stability. Moreover, disruption of autophagy-related genes accelerates tumorigenesis in animals. However, autophagy may also act as a prosurvival mechanism to protect cancer cells from various forms of cellular stress. In cancer therapy, adaptive autophagy in cancer cells sustains tumor growth and survival in face of the toxicity of cancer therapy. To this end, inhibition of autophagy may sensitize cancer cells to chemotherapeutic agents and ionizing radiation. Nevertheless, in certain circumstances, autophagy mediates the therapeutic effects of some anticancer agents. Data from recent studies are beginning to unveil the apparently paradoxical nature of autophagy as a cellfate decision machinery. Taken together, modulation of autophagy is a novel approach for enhancing the efficacy of existing cancer therapy, but its Janus-faced nature may complicate the clinical development of autophagy modulators as anticancer therapeutics.

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Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions

Cited by 132 publications

References 42 publications

Autophagy patterns and prognosis in uveal melanomas

Autophagy patterns and prognosis in uveal melanomas

Beclin 1 restrains tumorigenesis through Mcl-1 destabilization in an autophagy-independent reciprocal manner

The autophagic paradox in cancer therapy

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