Phosphoserine phosphatase (PSPH), a key enzyme of the l‐serine synthesis pathway, has been involved in cancer progression and survival. However, limited evidence revealed the PSPH influence on hepatocellular carcinoma (HCC). Herein, we observed that PSPH expression was upregulated in both HCC tissues and cell lines, which was determined by western blotting. TCGA database showed that the PSPH protein levels were significantly upregulated and affected patient survival rates in HCC. Then gain‐ and loss‐of‐function manipulations were performed by transfection with a pcDNA‐PSPH expression vector or a specific short interfering RNA against PSPH in Huh7 cells. Huh7 cell proliferation, stemness, invasion, and apoptosis were assessed by using CCK‐8 test, colony formation assay, Transwell assay, and Flow cytometry analysis, respectively, and levels of autophagy‐related proteins were detected by using western blotting. The results showed that PSPH could induce Huh7 cell autophagy, promote cell proliferation and invasion, and inhibit apoptosis. The knockdown of PSPH could inhibit Huh7 cell proliferation, invasion, and autophagy. Furthermore, PSPH activated Liver kinase B1 (LKB1) and TGF beta‐activated kinase 1 (TAK1), affected the adenosine 5′‐monophosphate‐activated protein kinase (AMPK)/mTOR/ULK1 signaling pathway, but could not activate calcium/calmodulin‐dependent protein kinase kinase (CaMKK) in Huh7 cells. Inhibition of either LKB1, TAK1, or AMPK could eliminate the effect of PSPH overexpression on Huh7 cell behaviors. However, inhibition of CaMKK could not influence the effect of PSPH overexpression on Huh7 cell behaviors. In conclusion, PSPH could induce autophagy, promote proliferation and invasion, and inhibit apoptosis in HCC cells via the AMPK/mTOR/ULK1 signaling pathway.

中文翻译：

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PSPH通过AMPK/mTOR/ULK1信号通路诱导肝癌细胞株Huh7细胞自噬并促进细胞增殖和侵袭

磷酸丝氨酸磷酸酶 (PSPH)，L的关键酶丝氨酸合成途径，已参与癌症进展和生存。然而，有限的证据揭示了 PSPH 对肝细胞癌 (HCC) 的影响。在此，我们观察到 PSPH 表达在 HCC 组织和细胞系中均上调，这是通过蛋白质印迹确定的。TCGA 数据库显示 PSPH 蛋白水平显着上调并影响 HCC 患者的存活率。然后通过在 Huh7 细胞中转染 pcDNA-PSPH 表达载体或针对 PSPH 的特定短干扰 RNA 进行功能获得和丧失操作。Huh7细胞增殖、干性、侵袭和凋亡分别通过CCK-8试验、集落形成试验、Transwell试验和流式细胞术分析进行评估，使用蛋白质印迹法检测自噬相关蛋白的水平。结果表明，PSPH可诱导Huh7细胞自噬，促进细胞增殖和侵袭，抑制细胞凋亡。PSPH 的敲低可以抑制 Huh7 细胞增殖、侵袭和自噬。此外，PSPH 激活肝激酶 B1 (LKB1) 和 TGF β 激活激酶 1 (TAK1)，影响腺苷 5'-单磷酸激活蛋白激酶 (AMPK)/mTOR/ULK1 信号通路，但不能激活钙/钙调蛋白- Huh7 细胞中的依赖性蛋白激酶激酶 (CaMKK)。抑制 LKB1、TAK1 或 AMPK 可以消除 PSPH 过表达对 Huh7 细胞行为的影响。然而，CaMKK 的抑制不能影响 PSPH 过表达对 Huh7 细胞行为的影响。总之，PSPH 可以诱导自噬，