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B7 同源物 3 通过 Raf/MEK/ERK 轴诱导乳腺癌肺转移。

B7 homolog 3 induces lung metastasis of breast cancer through Raf/MEK/ERK axis.

机构信息

Department of Radiotherapy, Affiliated Hospital of Weifang Medical University, No. 2428, Yuhe Road, Weifang, 261031, Shandong Province, China.

Department of Intervention, The Affiliated Weihai Second Municipal Hospital of Qingdao University, Weihai, 264200, China.

出版信息

Breast Cancer Res Treat. 2022 Jun;193(2):405-416. doi: 10.1007/s10549-022-06520-8. Epub 2022 Mar 21.

DOI:10.1007/s10549-022-06520-8
PMID:35312883
Abstract

PURPOSE

The essential action of B7 homolog 3 (B7-H3) in different diseases and cancers has been documented. We here focused on its role in breast cancer through the Raf/MEK/ERK axis regarding lung metastasis.

METHODS

Expression pattern of B7-H3 was determined in breast cancer tissues and cells with its correlation with prognosis analyzed. Then, through transfection of lentivirus vector expressing B7-H3-shRNA, overexpression vector of B7-H3 (B7-H3-LV), U0126 (small molecule inhibitor of MEK), or PD98059 (small molecule inhibitor of ERK), the in vitro and in vivo effects of B7-H3 in breast cancer cell biological processes, and lung metastasis were analyzed in relation to the Raf/MEK/ERK axis.

RESULTS

We discovered elevated B7-H3 in breast cancer and its elevation associated with poor prognosis. B7-H3 promoted the malignant properties of breast cancer cells, accompanied with increased N-cadherin and vimentin and reduced E-cadherin. Additionally, overexpression of B7-H3 accelerated the lung metastasis in breast cancer in vivo. All the above promoting action of B7-H3 was achieved through activation of the Raf/MEK/ERK signaling pathway.

CONCLUSION

Taken together, B7-H3 can promote lung metastasis in breast cancer through activation of the Raf/MEK/ERK axis.

摘要

目的

B7 同源物 3（B7-H3）在不同疾病和癌症中的基本作用已有相关文献记载。我们主要关注其在乳腺癌中的作用，特别是关于肺转移的 Raf/MEK/ERK 轴。

方法

通过检测 B7-H3 在乳腺癌组织和细胞中的表达模式，并分析其与预后的相关性，来确定 B7-H3 的表达模式。然后，通过转染表达 B7-H3-shRNA 的慢病毒载体、B7-H3 的过表达载体（B7-H3-LV）、U0126（MEK 的小分子抑制剂）或 PD98059（ERK 的小分子抑制剂），分析 B7-H3 在乳腺癌细胞生物学过程中的体外和体内作用，以及与 Raf/MEK/ERK 轴相关的肺转移情况。

结果

我们发现乳腺癌中 B7-H3 的表达水平升高，且其升高与预后不良相关。B7-H3 促进了乳腺癌细胞的恶性特性，伴随着 N-钙黏蛋白和波形蛋白的增加和 E-钙黏蛋白的减少。此外，B7-H3 的过表达还加速了乳腺癌在体内的肺转移。B7-H3 的所有上述促进作用都是通过激活 Raf/MEK/ERK 信号通路来实现的。

结论

综上所述，B7-H3 通过激活 Raf/MEK/ERK 轴促进乳腺癌的肺转移。

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Bull Cancer. 2021 Mar;108(3):323-332. doi: 10.1016/j.bulcan.2020.10.022. Epub 2021 Jan 8.
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Overdiagnosis and Risks of Breast Cancer Screening.
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