High LC3 expression correlates with poor survival in patients with oral squamous cell carcinoma

Tang, Jen‐Yang; Hsi, Edward; Huang, Ya‐Chun; Hsu, Nancy; Chu, Pei‐Yi; Chai, Chee‐Yin

doi:10.1016/j.humpath.2013.06.017

Cited by 53 publications

(36 citation statements)

References 25 publications

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“…However, the association between Beclin-1 expression and the clinicopathological characteristics of different tumors is complex, and under debate. A number of studies have demonstrated that the high expression of Beclin-1, as confirmed by immunohistochemistry, is correlated with unfavorable clinicopathological parameters (3,16,17); however, other studies concluded that the pathogenesis and progression of cancer were associated with reduced Beclin-1 expression, which is consistent with the present study (6,9,18). These data indicated that Beclin-1 may induce different effects in different types of tumors, depending on the intrinsic characteristics of the tumors themselves.…”

Section: Discussionsupporting

confidence: 89%

Beclin‑1 suppresses gastric cancer progression by promoting apoptosis and reducing cell migration

et al. 2017

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Abstract. To investigate Beclin-1 expression in gastric cancer and its clinical relevance, 60 samples were collected from patients with gastric carcinoma, which were subjected to immunohistochemical staining and analysis. Associations of Beclin-1 expression with the clinical parameters of the patients, including tumor size, histological differentiation and metastatic status, were examined by statistical analysis. The results demonstrated that Beclin-1 expression in gastric carcinoma tissue was significantly associated with the tumor, node, metastasis stage and tumor invasion status. Further experiments indicated that Beclin-1 overexpression promoted MKN-45 gastric cancer cell apoptosis and inhibited their migration. These data suggested that Beclin-1 was a suppressor of tumorigenesis in gastric cancer and a potential therapeutic target for patients with gastric cancer. IntroductionAutophagy serves an important role in maintaining cell metabolism and homeostasis (1). Autophagy is a process of endogenous substrate digestion in cells; autophagosomes are formed, and mature proteins or damaged organelles in the cytoplasm are encased by lysosomes, in which lysosomal proteases degrade them.During tumorigenesis and tumor progression, autophagy exerts its role as a tumor suppressor by removing abnormally folded proteins and dysfunctional organelles such as mitochondria, inhibiting cell stress responses (2). However, in instances of nutritional deficiencies and hypoxia, autophagy supports tumor cell survival, which promotes cell proliferation and suppresses cell death (3). Compromised autophagy promotes chromosomal instability, including increased DNA damage, gene amplification and aneuploidy (4).As a key autophagy regulator associated with apoptosis and differentiation, the autophagy-associated protein Beclin-1 has been demonstrated to be involved in many types of cancer, including ovarian carcinoma (5), hepatocellular carcinoma (6), melanoma (7), rectal cancer (8) and tongue squamous cell carcinoma (9). It has been suggested that the endogenous Beclin-1 protein expression is frequently low in human breast epithelial carcinoma cell lines and tissues, whereas it is expressed ubiquitously at high levels in normal breast epithelia (10). Concomitantly, the autophagy-promoting activity in the MCF7 breast cancer cell line following transfection with Beclin-1 was observed to inhibit MCF7 proliferation, clonogenicity and tumorigenesis (10). A previous in vivo study demonstrated that mice with inactivated or deleted Beclin-1 were susceptible to tumors including lymphoma, lung cancer and liver cancer (11,12).Beclin-1 modulates cancer initiation and progression by affecting a wide range of pathological events, including extracellular matrix degradation, epithelial-to-mesenchymal transition, tumor angiogenesis and alterations to the tumor microenvironment (13). However, the effect of Beclin-1 in cancer development is complex, as a number of reports have indicated the pro-neoplastic and anti-neoplastic functions for Beclin-1, as revi...

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Section: Discussionsupporting

confidence: 89%

Beclin‑1 suppresses gastric cancer progression by promoting apoptosis and reducing cell migration

et al. 2017

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“…In HNSCC, increased levels of autophagy marker LC3 is associated with reduced overall survival (36). However, no studies have examined the therapeutic potential of autophagy inhibition in HNSCC.…”

Section: Resultsmentioning

confidence: 99%

“…Pathologic immunohistochemistry identification of autophagy markers in patient tissue has given mixed results, with some studies indicating a favorable outcome with increased expression of autophagic markers and others indicating an unfavorable outcome (36,40). We identify that LC3 puncta were significantly increased in HNSCC fibroblasts as compared to normal specimens from cancer-free patients (Fig 7A).…”

Section: Resultsmentioning

confidence: 99%

Secretory Autophagy in Cancer-Associated Fibroblasts Promotes Head and Neck Cancer Progression and Offers a Novel Therapeutic Target

et al. 2017

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Despite therapeutic advancements, there has been little change in the survival of patients with head and neck squamous cell carcinoma (HNSCC). Recent results suggest that cancer-associated fibroblasts (CAF) drive progression of this disease. Here, we report that autophagy is upregulated in HNSCC-associated CAFs where it is responsible for key pathogenic contributions in this disease. Autophagy is fundamentally involved in cell degradation, but there is emerging evidence that suggests it is also important for cellular secretion. Thus, we hypothesized that autophagy-dependent secretion of tumor-promoting factors by HNSCC-associated CAFs may explain their role in malignant development. In support of this hypothesis, we observed a reduction in CAF-facilitated HNSCC progression after blocking CAF autophagy. Studies of cell growth media conditioned after autophagy blockade revealed levels of secreted IL-6, IL-8 and other cytokines were modulated by autophagy. Notably, when HNSCC cells were co-cultured with normal fibroblasts they upregulated autophagy through IL-6, IL-8 and bFGF. In a mouse xenograft model of HNSCC, pharmacological inhibition of Vps34, a key mediator of autophagy, enhanced the antitumor efficacy of cisplatin. Our results establish an oncogenic function for secretory autophagy in HNSCC stromal cells that promotes malignant progression.

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“…In the present study, our results showed that the positive expression of LC3 in SACC was significantly higher when compared with normal salivary gland and pleomorphic adenoma. In human oral squamous cell carcinoma [9], elevated LC3 expression was found to be significantly associated with clinical and pathological characteristics of patients. LC3 was involved in the development and progression of prostate cancer and benign prostatic hyperplasia, indicating that autophagy may be a useful way to reduce the risk of prostate cancer [15].…”

Section: Discussionmentioning

confidence: 97%

“…Lysosome associated membrane protein 2 (LAMP2) is an important protein in the chaperone mediated autophagy pathway, it is a selective autophagy that is responsible for the lysosomal degradation of approximately 30 % of the modified and oxidatively damaged soluble cytosolic proteins that contain the recognizable peptide sequence motif [6]. Expression of LC3 and LAMP2 has been studied in many kinds of cancer, and over-expressed LC3 and LAMP2 were correlated with clinicopathologic characteristics [6][7][8][9]. As for the role of autophagy in cancer, it is still very controversial whether it promotes carcinogenesis and development or suppresses tumor growth by preventing the accumulation of damaged proteins and organelles.…”

mentioning

confidence: 99%

Expression of LC3, LAMP2, KEAP1 and NRF2 in Salivary Adenoid Cystic Carcinoma

Huang

Deng

Zhang

et al. 2015

Pathol. Oncol. Res.

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Salivary Adenoid Cystic Carcinoma (SACC) is a tumor characterized by inevitable local progression and terminal hematogenous metastasis. This study aimed to investigate the expression of LC3, LAMP2, KEAP1 and NRF2 in SACC. Human salivary gland tissue microarray which contains 74 SACC, 12 pleomorphic adenoma and 18 normal salivary gland specimens. High expression of LC3, LAMP2, KEAP1 and NRF2 were found in SACC patients, and LC3, LAMP2, KEAP1 and NRF2 expression were significantly higher in SACC than as compared with pleomorphic adenoma and (or) normal salivary gland. The expression of NRF2 was correlated with pathological type of human SACC (P < 0.05). Moreover, the high-expression of KEAP1 had significant correlations with LC3 (P < 0.001, R = 0.3195), and LAMP2 (P < 0.001, R = 0.3346) and NRF2 (P < 0.05, R = 0.2246) by using the Pearson correlation coefficient test. Our findings demonstrated that up-regulation of LC3, LAMP2, KEAP1 and NRF2 were associated with carcinogenesis and progression of SACC patients, suggesting that they may be useful molecular targets in salivary adenoid cystic carcinoma.

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High LC3 expression correlates with poor survival in patients with oral squamous cell carcinoma

Cited by 53 publications

References 25 publications

Beclin‑1 suppresses gastric cancer progression by promoting apoptosis and reducing cell migration

Beclin‑1 suppresses gastric cancer progression by promoting apoptosis and reducing cell migration

Secretory Autophagy in Cancer-Associated Fibroblasts Promotes Head and Neck Cancer Progression and Offers a Novel Therapeutic Target

Expression of LC3, LAMP2, KEAP1 and NRF2 in Salivary Adenoid Cystic Carcinoma

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