Pseudophosphatase STYX is induced by Helicobacter pylori and promotes gastric cancer progression by inhibiting FBXO31 function.
Pseudophosphatase STYX is induced by Helicobacter pylori and promotes gastric cancer progression by inhibiting FBXO31 function.
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伪磷酸酶 STYX 由幽门螺杆菌诱导，通过抑制 FBXO31 功能促进胃癌进展
DOI：
10.1038/s41419-022-04696-x
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发表时间：
2022-03-25
影响因子：
9
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Liu J;Zang Y;Ma C;Wang D;Tian Z;Xu X;Li W;Jia J;Liu Z
胃癌是世界上最常见的恶性肿瘤之一，在癌症相关死亡中排名第三。无催化活性的假磷酸酶STYX（丝氨酸/苏氨酸/酪氨酸相互作用蛋白）是蛋白酪氨酸磷酸酶家族的成员。最近有报道STYX在不同类型的癌症中作为潜在的癌基因发挥作用。然而，STYX在GC中的潜在作用和调节机制尚不清楚。在本研究中，我们发现STYX在胃癌组织中的表达高于癌旁组织，并且与胃癌患者的预后密切相关。STYX过表达促进GC细胞的增殖和迁移，而STYX敲低则具有相反的作用。裸鼠实验表明，STYX基因在GC细胞中的敲低显著抑制了体内肿瘤生长和肺转移。在机制上，我们的研究结果表明，STYX与F-box蛋白FBXO 31相互作用，破坏FBXO 31对其靶蛋白CyclinD 1和Snail 1的降解功能，从而增加GC中CyclinD 1和Snail 1的水平。STYX介导的生物学变化可以通过STYX和FBXO 31在GC细胞中的共表达来逆转。另外，转录因子c-Jun可增强STYX在胃癌中的表达。幽门螺杆菌（Helicobacter pylori，H. pylori）感染。总之，我们目前的研究表明，STYX通过抑制FBXO 31功能在GC中发挥致癌作用，并代表了GC中潜在的治疗靶点和预后生物标志物。
Gastric cancer (GC) is one of the most common malignancies in the world and ranks third in terms of cancer-related deaths. The catalytically inactive pseudophosphatase STYX (serine/threonine/tyrosine interacting protein) is a member of the protein tyrosine phosphatase family. It has been recently reported that STYX functions as a potential oncogene in different types of cancers. However, the potential role and regulatory mechanism of STYX in GC remains unknown. In this study, we find that STYX is highly expressed in GC tissues compared with adjacent noncancerous tissues and closely correlates with the prognosis of GC patients. STYX overexpression facilitates the proliferation and migration in GC cells, whereas STYX knockdown has the opposite effects. Nude mice experiments indicate that STYX knockdown in GC cells dramatically suppresses the tumor growth and lung metastasis in vivo. Mechanically, our results suggest that STYX interacts with the F-box protein FBXO31 and disrupts the degradation function of FBXO31 to its target proteins CyclinD1 and Snail1, thereby increasing the level of CyclinD1 and Snail1 in GC. STYX-mediated biological changes can be reversed by the co-expression of STYX and FBXO31 in GC cells. In addition, transcription factor c-Jun can enhance the expression of STYX in GC. The expression of STYX can also be induced by Helicobacter pylori (H. pylori) infection in c-Jun-dependent manner. Together, our present study suggests that STYX plays an oncogenic role in GC by inhibiting FBXO31 function and represents a potential therapeutic target and prognostic biomarker in GC.
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