B7-H3-Induced Signaling in Lung Adenocarcinoma Cell Lines with Divergent Epidermal Growth Factor Receptor Mutation Patterns.
B7-H3-Induced Signaling in Lung Adenocarcinoma Cell Lines with Divergent Epidermal Growth Factor Receptor Mutation Patterns.
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DOI：
10.1155/2020/8824805
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发表时间：
2020
影响因子：
--
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Ding M;Liao H;Zhou N;Yang Y;Guan S;Chen L
协同信号分子B7-H3由于在多种恶性肿瘤中的异常表达和丰富的信号转导途径而受到关注。B7-H3诱导的信号传导包括至少三个级联：PI 3 K/AKT、JAK 2/STAT 3和Raf/MEK/ERK 1/2，它们也参与肺腺癌细胞中表皮生长因子受体（EGFR）触发的信号传导。然而，B7-H3诱导的信号传导和EGFR信号传导之间的相关性，以及B7-H3靶向免疫治疗和EGFR靶向治疗在肺腺癌中的相关性仍有待阐明。在此我们发现B7-H3基因敲除降低了H3255和HCC 827细胞的细胞存活率，并增加了EGFR酪氨酸激酶抑制剂吉非替尼的敏感性，这两种肺腺癌细胞系分别携带EGFR L 858 R（外显子21）和Del E746-A750（外显子19）突变。B7-H3缺失导致H3255细胞中AKT和STAT 3磷酸化水平显著降低，而HCC 827细胞中AKT、STAT 3和ERK 1/2具有轻度至中度抑制。吉非替尼对H3255和HCC 827细胞中B7-H3缺失的作用相似。此外，B7-H3消融与吉非替尼在HCC 827细胞中具有显著的协同作用。总的来说，我们的研究揭示了B7-H3在具有不同EGFR突变的肺腺癌细胞系中诱导的信号传导，以及B7-H3和EGFR联合靶向治疗具有EGFR Del E746-A750突变的肺腺癌的翻译潜力。
The cosignal molecule B7-H3 is gaining attention due to its abnormal expression and abundant signal transduction in many types of malignancies. B7-H3-induced signaling includes at least three cascades: PI3K/AKT, JAK2/STAT3, and Raf/MEK/ERK1/2, which are also involved in epidermal growth factor receptor- (EGFR-) triggered signaling in lung adenocarcinoma cells. However, the correlation between B7-H3-induced signaling and EGFR signaling, and between B7-H3-targeted immunotherapy and EGFR-targeted therapy in lung adenocarcinoma, remains to be elucidated. Herein we find that knockout of B7-H3 gene decreased cell survival and increased EGFR-tyrosine kinase inhibitor gefitinib susceptibility of both H3255 and HCC827 cells, two lung adenocarcinoma cell lines harboring EGFR L858R (exon 21) and Del E746-A750 (exon 19) mutations, respectively. B7-H3 deletion resulted in dramatic reduction of phosphorylation level of AKT and STAT3 in H3255 cells while having mild-to-moderate suppression on AKT, STAT3, and ERK1/2 in HCC827 cells. Gefitinib had similar effects with B7-H3 deletion both in H3255 and HCC827 cells. Furthermore, B7-H3 ablation had significant synergistic effects with gefitinib in HCC827 cells. Collectively, our study reveals B7-H3-induced signaling in lung adenocarcinoma cell lines with divergent EGFR mutations, and a translational potential of combined targeted therapy of B7-H3 and EGFR in lung adenocarcinoma with EGFR Del E746-A750 mutation.
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影响因子：
11.2
作者：
Lazzara MJ;Lane K;Chan R;Jasper PJ;Yaffe MB;Sorger PK;Jacks T;Neel BG;Lauffenburger DA
通讯作者：
Lauffenburger DA
影响因子：
5.8
作者：
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通讯作者：
Sun DX
影响因子：
2.2
作者：
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通讯作者：
Weideman, Soeren A.
影响因子：
20.4
作者：
Qu, Yang;Emoto, Katsura;Travis, William D.
通讯作者：
Travis, William D.
影响因子：
4
作者：
Zhong, Chuanhong;Tao, Bei;Chen, Ligang
通讯作者：
Chen, Ligang