RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-intrinsic KLRC1 exerts tumor-suppressive functions in colorectal cancer.
Tumor-intrinsic KLRC1 exerts tumor-suppressive functions in colorectal cancer.
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结肠腺癌(COAD)是胃肠道中一种常见的恶性肿瘤,具有显著的发病率和死亡率,且大多数患者在诊断时已处于中晚期。杀伤细胞凝集素样受体C1基因(KLRC1)是NKG2受体家族中的一种抑制性受体,可被HLA-E识别,从而抑制NK细胞的细胞毒活性和细胞因子分泌。然而,其在包括COAD在内的多种癌症中的功能知之甚少。在本研究中,我们揭示了COAD中KLRC1表达降低与不良预后、欠佳的组织学特征和更晚期的病理分期相关。此外,KLRC1表达可独立预测COAD患者的疾病进展。根据功能富集分析,KLRC1与免疫应答和细胞增殖相关的信号通路有关。此外,我们验证了KLRC1在COAD细胞系中表达下调,且KLRC1过表达显著降低了COAD细胞系的迁移、侵袭和增殖能力以及异种移植肿瘤生长。我们的研究阐明了KLRC1是COAD的一种新型预后标志物和治疗靶点。
Colon adenocarcinoma (COAD) represents a prevalent malignant neoplasm within the gastrointestinal tract characterized by significant morbidity and mortality rates, and the majority of patients are in intermediate to advanced stages at the time of diagnosis. Killer cell lectin-like receptor C1 gene (KLRC1) is an inhibitory receptor in the NKG2 receptor family that can be recognized by HLA-E, thereby inhibiting cytotoxic activity and cytokine secretion from NK cells.
However, little is known about its function in various cancers, including COAD. In the present study, we revealed that reduced expression of KLRC1 in COAD correlates with adverse prognosis, suboptimal histological characteristics, and more advanced pathological staging.
In addition, KLRC1 expression independently predicted progression in COAD patients. According to the functional enrichment analysis, KLRC1 has been implicated in signaling pathways related to the immune response and cellular proliferation.
In addition, we verified that KLRC1 was down-regulated in COAD cell lines and that the overexpression of KLRC1 significantly reduced the migration, invasion, and proliferation capacities and xenograft tumor growth of COAD cell lines.
Our study elucidates that KLRC1 is a novel prognostic marker and a therapeutic target for COAD.
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