PPDPF promotes lung adenocarcinoma progression via inhibiting apoptosis and NK cell-mediated cytotoxicity through STAT3
PPDPF promotes lung adenocarcinoma progression via inhibiting apoptosis and NK cell-mediated cytotoxicity through STAT3
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PPDPF 通过 STAT3 抑制细胞凋亡和 NK 细胞介导的细胞毒性，促进肺腺癌进展
DOI：
10.1038/s41388-022-02418-3
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发表时间：
2022-07-29
期刊：
影响因子：
8
通讯作者：
Li，Jing-Jing
中科院分区：
文献类型：
--
作者：
Zheng，Qian-Wen;Ni，Qian-Zhi;Li，Jing-Jing
肺癌是世界上最常见的恶性肿瘤，也是癌症死亡的主要原因，而肺腺癌（LUAD）是最常见的亚型。考虑到耐药性的出现，迫切需要开发更有效的治疗方法来改善预后。在这里，我们报道了胰腺祖细胞分化和增殖因子（PPDPF）缺乏在体外和体内抑制LUAD的发展。机制上，PPDPF通过干扰STAT3- ptpn1相互作用诱导STAT3过度活跃。激活STAT3可促进BMPR2转录，进一步抑制细胞凋亡。此外，PPDPF减少NK细胞的浸润和活化，形成免疫抑制微环境，这也是由STAT3介导的。此外，我们发现PPDPF的表达与LUAD的恶性特征以及临床样本中BMPR2和p-STAT3水平呈正相关。因此，我们的研究提示PPDPF通过调节STAT3活性，正向调节BMPR2表达，促进免疫逃逸，为LUAD提供了潜在的治疗靶点。
Lung cancer is the most common malignancy and the leading cause of cancer death worldwide, and lung adenocarcinoma (LUAD) is the most prevalent subtype. Considering the emergence of resistance to therapies, it is urgent to develop more effective therapies to improve the prognosis. Here we reported that pancreatic progenitor cell differentiation and proliferation factor (PPDPF) deficiency inhibited LUAD development both in vitro and in vivo. Mechanistically, PPDPF induces hyperactive STAT3 by interfering STAT3-PTPN1 interaction. Activated STAT3 promoted BMPR2 transcription, which further inhibited apoptosis. Moreover, PPDPF reduced NK cell infiltration and activation to develop an immunosuppressive microenvironment, which was also mediated by STAT3. Furthermore, we identified that the expression of PPDPF was positively correlated with the malignant features of LUAD, as well as BMPR2 and p-STAT3 level in clinical samples. Therefore, our study suggests that PPDPF positively regulates BMPR2 expression and facilitates immune escape via regulating STAT3 activity, providing a potential therapy target for LUAD.