Inverse correlation between microtubule‐associated protein 1A/1B‐light chain 3 and p62/sequestosome‐1 expression in the progression of cutaneous squamous cell carcinoma

Abstract

The expression of autophagy-related markers has occasionally been reported to correlate with the clinical stage of disease in patients with solid cancer, indicating autophagy activation. However, there have been no such reports for cutaneous squamous cell carcinoma. In this study, we investigated the expression levels of two autophagy-related markers, microtubule-associated protein IA/IB light chain 3 (LC3) and p62/sequestosome-1 (p62), in cutaneous squamous cell carcinoma specimens and assessed their correlation to clinicopathological factors in patients with this type of cancer. As a marker of the autophagosome, LC3 expression increases with autophagosome formation/accumulation, whereas p62 expression decreases due to selective degradation via autophagy. We performed immunostaining for LC3 and p62 in 50 cutaneous squamous cell carcinoma specimens obtained from patients treated by surgical resection, counted the number of cells that showed positive staining, and calculated the percentage of positive cells per low-power microscopic field. We next investigated the correlations between the expression levels of these markers and various clinicopathological factors. The results indicated that LC3 expression increased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.046). By contrast, the expression of p62 decreased significantly with advanced clinical stage (P < 0.001) and increased tumor diameter (P = 0.001). These results suggest that autophagy becomes activated during disease progression in patients with cutaneous squamous cell carcinoma.

Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

“…However, other investigations reported the protumoral activity of autophagy in skin cancer. In this line, an increased expression of the autophagy marker LC3 has been demonstrated in patients with SCC, which was associated with disease progression and prognosis of cancer [ 300 ]. Interestingly, an in vitro study showed that the inhibition of both Akt signaling and autophagy by the lysosomal inhibitor chloroquine enhanced the susceptibility of metastatic SCC cells to docetaxel-induced apoptosis [ 301 ].…”

RNA-Seq and ChIP-Seq Reveal SQSTM1/p62 as a Key Mediator of JunB Suppression of NF-κB-Dependent Inflammation

“…SQSTM1 is implicated in cancers of various organs, including kidney( Li et al , 2013 ), tuberous sclerosis complex ( Parkhitko et al , 2011 ), pancreatic ( Ling et al , 2012 ), prostate ( Chang et al , 2014 ), lung( Inoue et al , 2012 ), and oral ( Inui et al , 2013 ; Kuo et al , 2014 ). However, in cutaneous squamous cell carcinoma, SQSTM1 displays an inverse correlation with malignant progression ( Yoshihara et al , 2014 ), suggesting that SQSTM1 may have epidermis-specific functions. Similar to SQSTM1, NF-κB is known to stimulate inflammation and tumorigenesis in a wide range of tissues.…”

Expression profiling analysis of autophagy-related genes in perineural invasion of cutaneous squamous cell carcinoma

“…Increasing evidence has demonstrated that tumorigenesis, progression, invasion and metastasis of SCC involve several signal transduction pathways and molecules, including Notch, Integrin, tumor protein p53 (p53), epidermal growth factor receptor (EGFR) ( 5 ). Recently, researchers have demonstrated that autophagy might play a pivotal role in the pathogenesis of cSCC ( 6 , 7 ). Autophagy (term here used generally for macroautophagy) is a homeostatic mechanism under starvation or stressful conditions, resulting in the degradation of aggregated proteins and damaged organelles, and subsequently buffering metabolic stress by recycling intracellular components ( 8 , 9 ).…”

“…Therefore, the relationship between autophagy and SCC pathogenesis and progression is complex. Previous studies have, however, indicated that autophagy-specific markers [high expression of Beclin 1 and/or microtubule-associated protein 1 light chain 3 (LC3), and lower level of p62/sequestosome-1] may serve a key role in controlling the tumorigenesis, progression and lymph-node metastasis of cSCC and may be prognostic predictors of clinical outcome ( 6 , 7 , 14 ).…”