PHGDH 通过 Wnt/β-catenin 通路促进食管鳞癌进展。
PHGDH promotes esophageal squamous cell carcinoma progression via Wnt/β-catenin pathway.
机构信息
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, PR China.
Department of Oncology, Changzhi People's Hospital, Changzhi, Shanxi 046000, PR China.
出版信息
Cell Signal. 2023 Sep;109:110736. doi: 10.1016/j.cellsig.2023.110736. Epub 2023 May 31.
PURPOSE
Esophageal squamous carcinoma (ESCC) with a high incidence in China, lacks effective therapeutic targets. Phosphoglycerate dehydrogenase (PHGDH) is a key enzyme in serine biosynthesis. However, the biological role of PHGDH in ESCC has not been revealed.
METHODS
The expression of PHGDH in ESCC was investigated by UALCAN. The relationship between PHGDH expression and its prognostic value was analyzed by Kaplan-Meier and univariate Cox regression. Further, the potential functions of PHGDH involved in ESCC were explored through DAVID database and GSEA software. In addition, the expression of PHGDH was verified in ESCC. Then, the effects of PHGDH knockdown on ESCC were evaluated in vitro and in vivo by cell proliferation, clone formation, cell cycle, apoptosis, tube formation assays and ESCC cells derived xenograft model. In addition, western blotting and immunohistochemistry were used to detect the expression of Wnt/β-catenin pathway which was associated with PHGDH.
RESULTS
Bioinformatics analysis found that PHGDH was highly expressed in ESCC, and meaningfully, patients with high PHGDH expression had a poor prognosis. Moreover, the overexpression of PHGDH was verified in ESCC. Afterwards, PHGDH knockdown inhibited the cell proliferation, induced cell cycle arrest and apoptosis in ESCC cells, and inhibited the angiogenesis of HUVECs induced by ESCC conditioned medium, as well as inhibited the growth of xenograft tumor. Mechanistically, PHGDH knockdown inhibited Wnt/β-catenin signaling pathway in ESCC.
CONCLUSION
High expression of PHGDH predicts a poor prognosis for ESCC. PHGDH knockdown inhibits ESCC progression by suppressing Wnt/β-catenin signaling pathway, indicating that PHGDH might be a potential target for ESCC therapy.
目的
在中国高发的食管鳞状细胞癌（ESCC）缺乏有效的治疗靶点。磷酸甘油酸脱氢酶（PHGDH）是丝氨酸生物合成的关键酶。然而，PHGDH 在 ESCC 中的生物学作用尚未被揭示。
方法
通过 UALCAN 研究 ESCC 中 PHGDH 的表达。通过 Kaplan-Meier 和单因素 Cox 回归分析 PHGDH 表达与预后价值的关系。此外，通过 DAVID 数据库和 GSEA 软件探索 PHGDH 参与 ESCC 的潜在功能。另外，验证 ESCC 中 PHGDH 的表达。然后，通过细胞增殖、克隆形成、细胞周期、凋亡、管形成测定和 ESCC 细胞衍生的异种移植模型评估 PHGDH 敲低对 ESCC 的影响。此外，使用 Western blot 和免疫组化检测与 PHGDH 相关的 Wnt/β-catenin 通路的表达。
结果
生物信息学分析发现 PHGDH 在 ESCC 中高表达，有意义的是，高 PHGDH 表达的患者预后较差。此外，在 ESCC 中验证了 PHGDH 的过表达。随后，PHGDH 敲低抑制 ESCC 细胞的增殖，诱导细胞周期停滞和凋亡，并抑制 ESCC 条件培养基诱导的 HUVEC 血管生成，以及抑制异种移植肿瘤的生长。在机制上，PHGDH 敲低抑制了 ESCC 中的 Wnt/β-catenin 信号通路。
结论
PHGDH 的高表达预示 ESCC 预后不良。PHGDH 敲低通过抑制 Wnt/β-catenin 信号通路抑制 ESCC 进展，表明 PHGDH 可能是 ESCC 治疗的潜在靶点。
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