title: Overexpression and altered subcellular localization of autophagy-related 16-like 1 in human oral squamous-cell carcinoma: correlation with lymphovascular invasion and lymph-node metastasis.
abstract: 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.
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nomura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamano
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Fushimi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishigami
authors.forename: Yukinao
authors.initials: Y
authors.lastname: Kouzu
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Koike
authors.forename: Masashi
authors.initials: M
authors.lastname: Siiba
authors.forename: Hiroki
authors.initials: H
authors.lastname: Bukawa
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yokoe
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kubosawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001343:Autophagy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: C111180:BCL9 protein, human; D009363:Neoplasm Proteins; D014157:Transcription Factors