The HPA/SDC1 axis promotes invasion and metastasis of pancreatic cancer cells by activating EMT via FGF2 upregulation
The HPA/SDC1 axis promotes invasion and metastasis of pancreatic cancer cells by activating EMT via FGF2 upregulation
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DOI：
10.3892/ol.2019.11121
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发表时间：
2020-01-01
期刊：
影响因子：
2.9
通讯作者：
Zhao, Haoliang
中科院分区：
文献类型：
--
作者：
Chen, Xidong;Zhao, Haichao;Zhao, Haoliang
胰腺癌的特点是没有早期特异性临床症状，伴有快速转移和侵袭。它是最常见的癌症类型之一，更重要的是，它是所有癌症类型中死亡率最高的最常见的恶性癌症类型之一。据报道，类肝素酶（HPA）/syndecan-1（SDC 1）轴可促进多种癌症类型的肿瘤生长、侵袭、转移和血管生成;然而，有关HPA/SDC 1轴在胰腺癌中的作用和机制的研究有限。本研究旨在探讨HPA/SDC 1轴在胰腺癌中的生物学功能及其临床意义。结果表明，HPA在胰腺癌组织和细胞系中升高，并且其高表达与不良预后相关。HPA通过上调SDC 1的表达来介导成纤维细胞生长因子2（FGF 2）表达的增加。相反，沉默HPA介导FGF 2表达的抑制。此外，观察到上调的FGF 2通过激活PI 3 K/Akt信号通路增加下游Palladin蛋白的表达，并且还导致上皮-间充质转化（EMT）的激活。随后，发现EMT促进胰腺癌细胞的迁移和侵袭。总之，HPA/SDC 1轴被揭示在FGF 2的调节中起重要作用，并且被发现促进胰腺癌细胞的侵袭和转移。这些发现表明HPA/SDC 1轴可作为胰腺癌的有效治疗靶点。
Pancreatic cancer is characterized by the absence of early specific clinical symptoms, accompanied with rapid metastasis and invasion. It is one of the most prevalent types of cancer and more importantly, one of the most common types of malignant cancer with the highest mortality rate of all cancer types. The heparanase (HPA)/syndecan-1 (SDC1) axis has been reported to promote tumor growth, invasion, metastasis and angiogenesis in a variety of cancer types; however, studies into the role and mechanism of the HPA/SDC1 axis in pancreatic cancer are limited. The present study aimed to investigate the biological function and clinical significance of the HPA/SDC1 axis in pancreatic cancer. The results demonstrated that HPA is elevated in pancreatic cancer tissues and cell lines, and that its high expression was associated with poor prognosis. HPA was revealed to mediate an increase in fibroblast growth factor 2 (FGF2) expression by upregulating the expression of SDC1. Conversely, silencing HPA mediated the suppression of FGF2 expression. Furthermore, upregulated FGF2 was observed to increase the expression of downstream Palladin proteins by activating the PI3K/Akt signaling pathway and also lead to the activation of epithelial-mesenchymal transition (EMT). Subsequently, EMT was found to promote the migration and invasion of pancreatic cancer cells. In summary, the HPA/SDC1 axis was revealed to serve an important role in the regulation of FGF2, and was found to promote the invasion and metastasis of pancreatic cancer cells. These findings indicated that the HPA/SDC1 axis may be used as an effective therapeutic target for pancreatic cancer.