Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway.
Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway.
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通过激活 Hippo 信号通路沉默 SAPCD2 抑制纤维肉瘤的增殖和肺转移
DOI：
10.3389/fonc.2020.574383
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发表时间：
2020
影响因子：
4.7
通讯作者：
Fan W
中科院分区：
文献类型：
--
作者：
Zhu B;Wu Y;Niu L;Yao W;Xue M;Wang H;Yang J;Li J;Fan W
与纤维肉瘤相关的主要问题是它有很高的转移到肺部的可能性。SAPCD2的异常表达已被广泛报道与多种癌症的进展和转移有关。然而，SAPCD2在纤维肉瘤中的临床意义和生物学作用尚不清楚。在此，我们报道了SAPCD2在纤维肉瘤组织中的表达显著升高，并且与几个原代成纤维细胞系相比，SAPCD2在纤维肉瘤细胞系中的表达显著上调。Kaplan-Meier生存分析显示，SAPCD2过表达与纤维肉瘤患者的早期进展、转移和预后不良显著相关。我们的结果进一步表明，沉默SAPCD2在体外抑制了纤维肉瘤细胞的增殖，增加了细胞的凋亡率。重要的是，沉默SAPCD2抑制了体内纤维肉瘤细胞的肺转移。进一步的机制研究表明，沉默SAPCD2通过激活Hippo信号通路抑制纤维肉瘤细胞的增殖和肺转移，发现结构性活性YAP1，YAP1-S127A显著逆转SAPCD2下调对纤维肉瘤细胞集落形成和贴壁非依赖性生长能力的抑制作用，以及对纤维肉瘤细胞凋亡率的刺激作用。综上所述，SAPCD2通过调节Hippo信号通路的活性促进纤维肉瘤细胞的增殖和肺转移，这一机制有望成为治疗肺转移性纤维肉瘤的潜在靶点。
The primary problem associated with fibrosarcoma is its high potential to metastasize to the lung. Aberrant expression of SAPCD2 has been widely reported to be implicated in the progression and metastasis in multiple cancer types. However, the clinical significance and biological roles of SAPCD2 in fibrosarcoma remain unknown. Here, we reported that SAPCD2 expression was markedly elevated in fibrosarcoma tissues, and its expression was differentially upregulated in fibrosarcoma cell lines compared with that in several primary fibroblast cell lines. Kaplan-Meier survival analysis revealed that SAPCD2 overexpression was significantly correlated with early progression and metastasis, and poor prognosis in fibrosarcoma patients. Our results further showed that silencing SAPCD2 inhibited the proliferation and increased the apoptosis of fibrosarcoma cells in vitro. Importantly, silencing SAPCD2 repressed lung metastasis of fibrosarcoma cells in vivo. Mechanistic investigation further demonstrated that silencing SAPCD2 inhibited the proliferation and lung metastasis of fibrosarcoma cells by activating the Hippo signaling pathway, as evidenced by the finding that constitutively active YAP1, YAP1-S127A, significantly reversed the inhibitory effect of SAPCD2 downregulation on the colony formation and anchorage-independent growth capabilities of fibrosarcoma cells, as well as the stimulatory effect on the apoptotic ratio of fibrosarcoma cells. In conclusion, SAPCD2 promotes the proliferation and lung metastasis of fibrosarcoma cells by regulating the activity of Hippo signaling, and this mechanism represents a potential therapeutic target for the treatment of lung metastatic fibrosarcoma.
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