Fibronectin 1 promotes melanoma proliferation and metastasis by inhibiting apoptosis and regulating EMT
Fibronectin 1 promotes melanoma proliferation and metastasis by inhibiting apoptosis and regulating EMT
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纤连蛋白1通过抑制细胞凋亡和调节EMT促进黑色素瘤增殖和转移
DOI：
10.2147/ott.s195703
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Jia, Lee
中科院分区：
文献类型：
--
作者：
Li, Bifei;Shen, Weiyu;Jia, Lee
背景和目的：癌症转移的复杂过程仍然是最不了解的。肿瘤细胞改变其蛋白质表达谱以从肿瘤转移中存活。纤维连接蛋白1（FN 1基因编码蛋白）是糖蛋白家族的成员，已被证明在癌症转移中起重要作用。然而，其对黑色素瘤转移的影响仍不清楚。方法：采用Western blot和RT-qPCR方法检测FN 1在原代细胞和转移细胞中的表达。并且，我们分析了FN 1在不同组织中的表达特征，并通过生物信息学分析来检测FN 1上调在黑色素瘤进展中的临床相关性。进一步通过小分子干扰RNA技术下调FN 1的表达，探讨FN 1对黑色素瘤表型及相关基因表达的影响。最后，我们使用生物信息学来揭示FN 1调节黑色素瘤进展的可能机制。结果：我们报道了FN 1的表达在黑色素瘤转移过程中发生了变化。在本研究中，我们通过小鼠模型建立了两个黑色素瘤转移细胞系，发现转移细胞具有更强的间充质表型，并具有更高的FN 1表达水平相比，原代细胞。此外，我们研究了上调的FN 1在肿瘤进展中的临床相关性。小干扰RNA（siRNA）介导的FN 1下调可抑制黑色素瘤细胞的迁移、侵袭、粘附、增殖能力并诱导细胞凋亡。我们检测到EMT相关基因签名减少，包括E-cadherin表达增加，N-cadherin和Vimentin表达减少。下调FN 1的表达也可增加Bax/Bcl-2的比值，可能导致黑色素瘤细胞凋亡。生物信息学分析表明，FN 1可能通过参与黏着斑和PI 3 K-Akt信号通路调控EMT过程和细胞凋亡。结论：总之，这些研究结果表明，FN 1在促进黑色素瘤转移的作用，通过抑制细胞凋亡和调节EMT。
Background and aims: The complex process of cancer metastasis remains the least understood. Tumor cells alter their protein expression profile to survive from the tumor metastasis. Fibronectin 1 (FN1 gene coding protein) is a member of the glycoprotein family that has been shown to play an important role in cancer metastasis. However, its effects on melanoma metastasis are still unclear. Methods: We detected the FN1 expression between metastatic cells and primary cells by using Western blot and RT-qPCR assays. And, we analyzed the expressed feature of FN1 in different tissues and examined the clinical relevance of upregulated FN1 in melanoma progression by bioinformatic analysis. Furthermore, we downregulated the expression of FN1 by small interfering RNA technique to reveal the effect of FN1 on melanoma phenotype and expression of related genes. Finally, we used bioinformatics to reveal the possible mechanism of FN1 regulating melanoma progression. Results: We reported that the expression of FN1 was changed during melanoma metastasis. In this study, we established two metastatic cell lines of melanoma through mouse model, and found that metastatic cells exhibited stronger mesenchyme phenotype and possessed higher FN1 expression level compared to primary cells. Besides, we examined the clinical relevance of upregulated FN1 in tumor progression. Small interfering RNA (siRNA)-mediated downregulation of FN1 suppressed the migration, invasion, adhesion, proliferation capabilities and induced apoptosis of melanoma cells. We detected a diminished EMT-related gene signature including increased expression of E-cadherin and decreased expression of N-cadherin and Vimentin. Downregulation of FN1 also increased Bax/Bcl-2 ratio which might result in apoptosis of melanoma cells. Bioinformatics analysis revealed that FN1 most likely involved in focal adhesion and PI3K-Akt signaling pathway to regulate EMT process and apoptosis. Conclusions: Taken together, these findings demonstrated a role of FN1 in promoting melanoma metastasis by inhibiting apoptosis and regulating EMT.