RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF-κB pathway in oral squamous cell carcinoma
RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF-κB pathway in oral squamous cell carcinoma
复制标题
在口腔鳞状细胞癌中，RACK1 通过 NF-κB 通路增加 M2/M1 巨噬细胞比率，从而促进癌症进展
DOI：
10.1002/1878-0261.12644
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发表时间：
2020-02-20
影响因子：
6.6
通讯作者：
Chen, Qianming
中科院分区：
文献类型：
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作者：
Dan, Hongxia;Liu, Sai;Chen, Qianming
活化C激酶受体1（Receptor for activated C kinase 1，RACK 1）可促进口腔鳞状细胞癌（oral squamous cell carcinoma，OSCC）的进展，RACK 1表达水平与OSCC患者的预后呈负相关。在这里，我们研究了RACK 1表达对肿瘤相关巨噬细胞的募集和分化的影响。RACK 1在口腔鳞状细胞癌细胞中的高表达与来自临床队列研究的肿瘤样本中M2巨噬细胞浸润增加相关。RACK 1表达与M2/M1比值联合检测可成功预测OSCC的预后。RACK 1高表达的OSCC细胞抑制THP-1细胞的迁移，促进体外M2样巨噬细胞极化，并增加异种移植小鼠模型中M2样巨噬细胞的比例。此外，在与RACK 1沉默的细胞上清液共培养的巨噬细胞中诱导M1和M2样巨噬细胞极化相关蛋白。机制研究表明，C-C基序趋化因子2（CCL 2）、C-C基序趋化因子5（CCL 5）、白细胞介素-6（IL-6）和白细胞介素-1（IL-1）的表达和分泌与RACK 1的表达密切相关。此外，阻断核因子-κ B（NF-κ B）可促进M2样巨噬细胞极化。这些结果表明RACK 1和M2/M1比值是OSCC预后不良的预测因子。RACK 1通过调节NF-κ B B而促进M2样极化，可作为抗肿瘤免疫的潜在治疗靶点。
Receptor for activated C kinase 1 (RACK1) has been shown to promote oral squamous cell carcinoma (OSCC) progression, and RACK1 expression levels have been negatively correlated with prognosis in patients with OSCC. Here, we investigated the impact of RACK1 OSCC expression on the recruitment and differentiation of tumor-associated macrophages. High RACK1 expression in OSCC cells correlated with increased M2 macrophage infiltration in tumor samples from a clinical cohort study. Moreover, the combination of RACK1 expression and the M2/M1 ratio could successfully predict prognosis in OSCC. OSCC cells with high RACK1 expression inhibited the migration of THP-1 cells, promoted M2-like macrophage polarization in vitro, and increased the proportion of M2-like macrophages in a xenograft mouse model. Moreover, both M1- and M2-like macrophage polarization-associated proteins were induced in macrophages cocultured with RACK1-silenced cell supernatant. A mechanistic study revealed that the expression and secretion of C-C motif chemokine 2 (CCL2), C-C motif chemokine 5 (CCL5), interleukin-6 (IL-6), and interleukin-1 (IL-1) are closely related to RACK1 expression. In addition, blocking nuclear factor-kappa B (NF-kappa B) could promote M2-like macrophage polarization. These results indicate that RACK1 and the M2/M1 ratio are predictors of a poor prognosis in OSCC. RACK1 promotes M2-like polarization by regulating NF-kappa B and could be used as a potential therapeutic target for antitumor immunity.