Lung cancer, especially lung adenocarcinoma, is one of the most common neoplasms worldwide. However, the mechanisms underlying its initiation, development, and metastasis are still poorly understood. Destrin (DSTN) is a member of ADF/cofilin family. Its detailed biological function remains unknown, although it is reported that DSTN is involved in cytoskeleton remodeling and regulation of actin filament turnover. Recent evidence has shown that high expression of cofilin-1 is associated with invasion and poor prognosis of several types of human tumors, but the detailed mechanism is still entirely unclear, particularly in lung cancer tumorigenesis and malignancy. Here, we report that DSTN was highly expressed in a mouse lung cancer model induced by urethane and in clinical lung adenocarcinoma tissue samples. Its expression level was positively correlated with cancer development, as well as metastasis to the liver and lymph nodes. Consistently, it was directly associated with the poor prognosis of lung adenocarcinoma patients. Furthermore, we also found that DSTN promotes cell proliferation, invasion, and migration in vitro, and facilitates subcutaneous tumor formation and lung metastasis via intravenous injection in vivo. Mechanically, DSTN associates with and facilitates nuclear translocation of β-catenin, which promotes epithelial-to-mesenchymal transition (EMT). Taken together, our results indicated that DSTN enhances lung cancer malignancy through facilitating β-catenin nuclear translocation and inducing EMT. Combined with multivariate analyses, DSTN might potentially serve as a therapeutic target and an independent prognostic marker of lung adenocarcinoma. Implications: This finding indicates that DSTN facilitates β-catenin nuclear translocation and promotes malignancy in lung adenocarcinoma.

中文翻译：

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Destrin 通过激活 Wnt/β-catenin 信号通路促进肺腺癌进展

肺癌，尤其是肺腺癌，是全世界最常见的肿瘤之一。然而，其发生、发展和转移的潜在机制仍知之甚少。Destrin (DSTN) 是 ADF/cofilin 家族的成员。其详细的生物学功能仍然未知，尽管据报道 DSTN 参与细胞骨架重塑和肌动蛋白丝周转的调节。最近的证据表明，cofilin-1 的高表达与几种类型的人类肿瘤的侵袭和预后不良有关，但具体机制仍完全不清楚，特别是在肺癌肿瘤发生和恶性肿瘤中。在这里，我们报告了 DSTN 在由氨基甲酸乙酯诱导的小鼠肺癌模型和临床肺腺癌组织样本中高度表达。它的表达水平与癌症的发展以及向肝脏和淋巴结的转移呈正相关。一致地，它与肺腺癌患者的不良预后直接相关。此外，我们还发现DSTN在体外促进细胞增殖、侵袭和迁移，并通过体内静脉注射促进皮下肿瘤形成和肺转移。在机械上，DSTN 与 β-连环蛋白的核易位相关并促进其核转位，从而促进上皮间质转化 (EMT)。总之，我们的结果表明 DSTN 通过促进 β-连环蛋白核易位和诱导 EMT 来增强肺癌的恶性程度。结合多变量分析，DSTN 可能作为肺腺癌的治疗靶点和独立的预后标志物。意义：这一发现表明 DSTN 促进 β-连环蛋白核易位并促进肺腺癌的恶性。