Investigating Metastasis-related Functions and Clinical Applications of ACTN4 in Lung Adenocarcinoma

• Main Authors: Hua-ChienChang, 張華倩
• Other Authors: Pao-Chi Liao
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/27895739857756297614

碩士 === 國立成功大學 === 環境醫學研究所 === 101 === Lung cancer is the leading cause of cancer related death worldwide. There is a lack of diagnostic tests that specifically address metastasis. In our previous research of comparison of cell secretomes with low and high metastatic abilities, Alpha-actinin-4 (ACTN4) exhibited high expression levels in the cell secretome with high metastatic ability. ACTN4 is one of the members in the ACTN family of binding filaments that preserve cytoskeletal structure and cell morphology. It is also known to have a critical role in transcriptional regulation; this suggests that ACTN4 may have an association with cancer metastasis. In this study, ACTN4 was investigated for its role in lung adenocarcinoma metastasis. Knockdown of ACTN4 expression in lung adenocarcinoma cell lines showed that ACTN4 was a critical mediator in the regulation of carcinoma invasion and cell migration. In the immunofluorescence and confocal microscopy studies, ACTN4 had an indirect effect on the distribution of Actin to plays an important role in the formation of a pseudopod or lamellipodium structure in the cell. Immunohistochemistry was also performed to study the expression levels of ACTN4 in tissues. We found that the ACTN4 expression significantly correlated with the staging of lung cancer; especially in T-staging and N-staging (which are the factors of metastasis progression). The expressed levels of ACTN4 were significantly higher in the tumor tissues than in the normal tissues. Furthermore, the plasma expression levels of ACTN4 in lung adenocarcinoma patients were significantly higher than in the normal controls by enzyme-linked immunosorbent assay. Our results suggest that ACTN4 protein has a significant association with lung cancer metastasis and thus may be a potential biomarker for early detection of lung adenocarcinoma metastasis.