PPDPF promotes esophageal squamous cell carcinoma progression by blocking PCCA binding to PCCB and inhibiting methionine catabolism

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2024-12-16 DOI:10.1016/j.canlet.2024.217402

Mengwei Li , Yi Zhang , Zhexin Wang , Kai Wang , Jie Gao , Haiyong Gu , Zimei Zeng , Haoyao Jiang , Qi Fan , Yuxue Zhang , Xudong Hu , Lingling Cui , Yuezhen Deng , Yifeng Sun

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引用次数: 0

Abstract

While metabolic reprogramming and remodeling of tumor microenvironment play important roles in the development of esophageal squamous cell carcinoma (ESCC), the mechanisms remain unclear. In this study, we found that pancreatic progenitor cell differentiation and proliferation factor (PPDPF) is upregulated in ESCC and its expression level is associated with lymph node metastasis. PPDPF was found to promote tumorigenesis, lymph node metastasis and distal metastasis of ESCC cells. Furthermore, the results of mass spectrometry analysis revealed that PPDPF interacts with PCCA, the subunit of the PCC, a key enzyme involved in the catabolism of methionine by the C-Vomit pathway. In addition, PPDPF increases methionine and SAM levels. Additionally, knockdown of PPDPF decreases the levels of methionine and SAM in vivo, and promotes the infiltration of CD8⁺ T cells in ESCC. Taken together, the results of this study suggest that PPDPF inhibits the interaction between PCCA and PCCB to downregulate methionine catabolism via the C-Vomit pathway, providing a new target for the treatment of ESCC.

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PPDPF通过阻断PCCA与PCCB结合和抑制蛋氨酸分解代谢促进食管鳞状细胞癌的进展。

虽然肿瘤微环境的代谢重编程和重塑在食管鳞状细胞癌（ESCC）的发展中起重要作用，但其机制尚不清楚。在本研究中，我们发现胰腺祖细胞分化和增殖因子（PPDPF）在ESCC中上调，其表达水平与淋巴结转移有关。发现PPDPF促进ESCC细胞的肿瘤发生、淋巴结转移和远端转移。此外，质谱分析结果显示PPDPF与PCC亚基pca相互作用，PCC亚基是通过C-Vomit途径参与蛋氨酸分解代谢的关键酶。此外，PPDPF增加蛋氨酸和SAM水平。此外，PPDPF的下调降低了体内蛋氨酸和SAM的水平，促进了ESCC中CD8+ T细胞的浸润。综上所述，本研究结果提示PPDPF抑制PCCA与PCCB相互作用，通过C-Vomit途径下调蛋氨酸分解代谢，为ESCC的治疗提供了新的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.