2014
DOI: 10.1038/jid.2013.497
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Prognostic Impact of p62 Expression in Cutaneous Malignant Melanoma

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Cited by 39 publications
(40 citation statements)
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“…Thus, based on our past and current studies as well as others, it can be proposed that cytoprotective autophagy represents a mechanism of danger-signalling suppression in dying melanoma cells [67]. Due to melanomas' addiction to autophagy [22], especially in late stage metastatic disease [22,68], autophagy inhibition appears to be a viable strategy to increase MEK-inhibition-induced cell death associated with danger-signalling, thus advocating the need for autophagy inhibitor-based trials in a BRAF V600E related context. Moreover, the recent clinical finding that single agent targeting of MEK was insufficient to elicit a durable response in patients, may further implicate the need for combination therapy.…”
Section: Discussionmentioning
confidence: 95%
“…Thus, based on our past and current studies as well as others, it can be proposed that cytoprotective autophagy represents a mechanism of danger-signalling suppression in dying melanoma cells [67]. Due to melanomas' addiction to autophagy [22], especially in late stage metastatic disease [22,68], autophagy inhibition appears to be a viable strategy to increase MEK-inhibition-induced cell death associated with danger-signalling, thus advocating the need for autophagy inhibitor-based trials in a BRAF V600E related context. Moreover, the recent clinical finding that single agent targeting of MEK was insufficient to elicit a durable response in patients, may further implicate the need for combination therapy.…”
Section: Discussionmentioning
confidence: 95%
“…Thus far, little is known about to what extent autophagy plays a role in nevus > melanoma progression and in melanoma in its early versus advanced stages. However, it has been reported that RGP, VGP, and in particular MGP melanomas express significantly lower levels of LC3 than nevi (30) and that median p62/ SQSTM1 expression levels are lower in American Joint Committee on Cancer (AJCC) stage III/IV than in AJCC stage I/II melanomas (31). This is in concordance with our finding that the two MGP melanoma cell lines, WM983-B and SK-MEL-5, that had received DMSO only, showed an LC3-positive phagosome signal in less than 1% of the cells and that the level of p62/ SQSTM1 expression in the DMSO-treated WM983-B cells was low.…”
Section: Discussionmentioning
confidence: 99%
“…Conversely, decreased levels of p62 reflect active autophagy, as observed in advanced stage melanomas where autophagy is commonly reactivated to enhance tumor survival (Figure 1A). Data from our lab have further defined p62 expression as a prognostic biomarker for melanoma where a stepwise increase in expression is observed in early AJCC stage melanomas (increased above basal levels in benign nevi and reflecting deregulated autophagy) but which is subsequently decreased in advanced metastatic tumors, consistent with the reactivation of autophagy and its paradoxical role in cancer [Figures 1B,C; (26)]. Furthermore, univariate analysis showed a significantly increased risk of metastasis in AJCC stage II tumors with low p62 expression (<20% median p62 expression) compared to those with high expression (>20% p62 expression) [Figure 1D; (26)].…”
mentioning
confidence: 81%
“…Each point represents the mean % of p62 positive cells. Horizontal lines representing median p62 expression levels indicate an increase in median p62 expression levels between benign nevi and AJCC stage I or II melanomas and a relative decrease in expression in advanced AJCC stages III and IV tumors (Kruskal–Wallis P  < 0.0001) (26). (C) Photomicrographs of immunohistochemical p62 expression and mean % in a melanocytic nevus or an eventual AJCC stage I, II, or IV melanoma.…”
mentioning
confidence: 99%
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