Nomura Hitomi, Uzawa Katsuhiro, Yamano Yukio, Fushimi Kazuaki, Ishigami Takashi, Kouzu Yukinao, Koike Hirofumi, Siiba Masashi, Bukawa Hiroki, Yokoe Hidetaka, Kubosawa Hitoshi, Tanzawa Hideki
Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
Hum Pathol. 2009 Jan;40(1):83-91. doi: 10.1016/j.humpath.2008.06.018. Epub 2008 Sep 11.
Autophagy is a dynamic process of subcellular degradation, which has recently sparked great interest because it is involved in various developmental processes and various diseases including cancer. Autophagy-related 16-like 1 is a component of a large protein complex essential for autophagosome formation. We previously applied proteomic methods to characterize differentially expressed proteins in oral squamous cell carcinoma cells and detected significantly high expression levels of autophagy-related 16-like 1 in oral squamous cell carcinoma-derived cell lines compared to human normal oral keratinocytes. In the current study, to further determine the potential involvement of autophagy-related 16-like 1 in oral squamous cell carcinoma, we evaluated the state of autophagy-related 16-like 1 protein expression in human oral premalignant lesions and primary oral squamous cell carcinomas, and correlated the results with clinicopathologic variables. Autophagy-related 16-like 1 immunoreaction was predominant in a variety of subcellular components of oral squamous cell carcinoma tissues, including the cytoplasm and plasma membrane of malignant cells (45% and 39%, respectively) and peritumoral and intratumoral stroma (52%), whereas all of the components in normal tissues had no or faint autophagy-related 16-like 1 expression. In addition, high stromal expression of autophagy-related 16-like 1 was associated significantly with lymphovascular invasion of tumor cells (P = .037) and positive lymph node status (P = .015). Furthermore, cytoplasmic and plasma membranous autophagy-related 16-like 1 were also expressed in abundance in the oral premalignant lesion cells (74% and 32%, respectively). Our finding suggests that dysregulation of autophagy-related 16-like 1 protein expression is a frequent and early event during oral carcinogenesis and could affect the malignant behavior of oral squamous cell carcinoma cells.
自噬是一种亚细胞降解的动态过程，最近引发了极大的关注，因为它参与了包括癌症在内的各种发育过程和多种疾病。自噬相关16样蛋白1是自噬体形成所必需的一种大型蛋白质复合物的组成部分。我们之前应用蛋白质组学方法来表征口腔鳞状细胞癌细胞中差异表达的蛋白质，并检测到与人类正常口腔角质形成细胞相比，自噬相关16样蛋白1在口腔鳞状细胞癌衍生的细胞系中表达水平显著升高。在当前研究中，为了进一步确定自噬相关16样蛋白1在口腔鳞状细胞癌中的潜在作用，我们评估了人类口腔癌前病变和原发性口腔鳞状细胞癌中自噬相关16样蛋白1的蛋白表达状态，并将结果与临床病理变量相关联。自噬相关16样蛋白1免疫反应在口腔鳞状细胞癌组织的多种亚细胞成分中占主导地位，包括恶性细胞的细胞质和质膜（分别为45%和39%）以及肿瘤周围和肿瘤内基质（52%），而正常组织中的所有成分均无自噬相关16样蛋白1表达或表达微弱。此外，自噬相关16样蛋白1的高基质表达与肿瘤细胞的淋巴管浸润（P = 0.037）和阳性淋巴结状态（P = 0.015）显著相关。此外，自噬相关16样蛋白1在口腔癌前病变细胞的细胞质和质膜中也大量表达（分别为74%和32%）。我们的发现表明，自噬相关16样蛋白1的蛋白表达失调是口腔癌发生过程中常见的早期事件，可能会影响口腔鳞状细胞癌细胞的恶性行为。
