| Summary: | 博士 === 長庚大學 === 臨床醫學研究所 === 104 === Autophagy is an important metabolic mechanism for eukaryotic cells to adapt stress. The relationship between autophagy and cancer is complex. The aim of the study was to inspect the role of autophagy in oral squamous cell carcinoma (OSCC), the major type of oral cancer. By evaluating the expression of autophagy markers, including ATG5, ATG9A, ATG16L, Beclin 1, Beclin 2, LC3A, LC3B, and p62/SQSTM1 (p62), in OSCC, premalignant lesion, and normal oral mucosa, the alteration of autophagy and their prognostic roles were investigated. The impacts of Beclin 1 and Beclin 2 alterations on autophagy and tumor growth were evaluated on an OSCC cell line. Our data revealed that autophagy-related proteins expressions were stronger in OSCC than those in premalignant lesion and in normal oral mucosa. Distinct pattern of several autophagy-related proteins was related to prognosis of OSCC. High cytoplasmic p62 expression accompanied with either a low or high LC3 expression, which indicated autophagy flux impairment under basal or activated autophagic activity, was associated with aggressive behavior in advanced OSCCs. In OSCC cells, overexpression of either Beclin 1 or Beclin 2 led to autophagy activation and increased clonogenic survival. In addition, knockdown of Beclin 2 impaired autophagy yet also increased clonogenic survival, suggesting Beclin2 may promote tumor cell growth through different pathways. In conclusion, our study showed that autophagy was altered during OSCC initiation and progression. Several autophagy-related proteins were associated with tumorigenesis, and autophagy flux impairment contributed to cancer progression in advanced OSCCs.
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