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.
摘要：
Anoikis相关基因（ARG）导致生物体表现出对anoikis的抗性，并与各种恶性肿瘤的不良预后结果有关。因此,在HCC中鉴定与失巢凋亡相关的关键靶基因至关重要。我们发现ARGs与HCC的预后和免疫反应显着相关。核心基因,通过体内和体外研究，SPP1显着促进了HCC的失巢凋亡抵抗和转移。PI3K-Akt-mTOR通路在HCC环境中的失巢凋亡抑制中起关键作用。我们的研究揭示了SPP1在增强PKCα磷酸化中的作用，进而激活PI3K-Akt-mTOR级联。此外,SPP1被确定为MDSCs和Tregs迁移的关键调节因子，直接影响他们的免疫抑制能力。这些结果表明，在肝癌中，SPP1通过调节MDSCs和Tregs促进抗失巢凋亡和促进免疫逃避。
