The resistance to anoikis, mediated by Spp1, and the evasion of immune surveillance facilitate the invasion and metastasis of hepatocellular carcinoma

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Apoptosis Pub Date : 2024-07-27 DOI:10.1007/s10495-024-01994-x

Zhengwei Zhang, Xiaoning Chen, Yapeng Li, Feng Zhang, Zhen Quan, Zhuo Wang, Yang Yang, Wei Si, Yuting Xiong, Jiaming Ju, Yu Bian, Shibo Sun

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Abstract

Anoikis-Related Genes (ARGs) lead to the organism manifesting resistance to anoikis and are associated with unfavorable prognostic outcomes across various malignancies.Therefore, it is crucial to identify the pivotal target genes related to anoikis in HCC .We found that ARGs were significantly correlated with prognosis and immune responses in HCC. The core gene, SPP1, notably promoted anoikis resistance and metastasis in HCC through both in vivo and in vitro studies. The PI3K-Akt-mTOR pathway played a critical role in anoikis suppression within HCC contexts. Our research unveiled SPP1’s role in enhancing PKCα phosphorylation, which in turn activated the PI3K-Akt-mTOR cascade. Additionally, SPP1 was identified as a key regulator of MDSCs and Tregs migration, directly affecting their immunosuppressive capabilities.These findings indicate that in HCC, SPP1 promoted anoikis resistance and facilitated immune evasion by modulating MDSCs and Tregs.

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由 Spp1 介导的对 anoikis 的抗性和对免疫监视的规避促进了肝细胞癌的入侵和转移

厌氧相关基因（ARGs）会导致机体表现出对厌氧的抵抗力，并与各种恶性肿瘤的不良预后结果相关。因此，确定与 HCC 中厌氧相关的关键靶基因至关重要。通过体内和体外研究，核心基因 SPP1 显著促进了 HCC 的耐药和转移。PI3K-Akt-mTOR通路在抑制HCC中的anoikis过程中发挥了关键作用。我们的研究揭示了 SPP1 在增强 PKCα 磷酸化方面的作用，而 PKCα 磷酸化反过来又激活了 PI3K-Akt-mTOR 级联。这些研究结果表明，在HCC中，SPP1通过调节MDSCs和Tregs促进了抗肿瘤能力并促进了免疫逃避。

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来源期刊

Apoptosis 生物-生化与分子生物学

CiteScore

9.10

自引率

4.20%

发文量

审稿时长

1 months

期刊介绍： Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.