Asporin Interacts With HER2 to Promote Thyroid Cancer Metastasis via the MAPK/EMT Signaling Pathway.
Asporin Interacts With HER2 to Promote Thyroid Cancer Metastasis via the MAPK/EMT Signaling Pathway.
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DOI：
10.3389/fonc.2022.762180
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
甲状腺癌的组织学亚型中约85%为乳头状甲状腺癌（PTC），由于淋巴结转移或远处转移，PTC患者的发病率和死亡率迅速增加。因此，需要进一步了解淋巴结转移或远处转移的PTC患者的发病机制。我们采用基于tmt的定量蛋白质组学方法来鉴定和分析不同程度淋巴结转移的PTC中差异表达的蛋白。与配对的正常组织相比，通过蛋白质组学、western blotting和免疫组化分析发现，在PTC-N0、PTC-N1a和PTC-N1b肿瘤组织中，阿霉素过表达。功能上，阿霉素主要表达于PTC肿瘤组织的细胞外基质、细胞膜和细胞质中，促进甲状腺癌细胞的增殖、迁移和侵袭。机制上，通过与HER2相互作用，使HER2在细胞膜和细胞质上共定位，并通过MAPK信号通路上调emt激活转录因子的表达。临床可将阿霉素作为鉴别PTC患者有无淋巴结转移的血清学生物标志物，而在PTC肿瘤组织中高表达是预后不良的危险因素。
Approximately 85% of histological subtypes of thyroid cancer are papillary thyroid cancer (PTC), and the morbidity and mortality of PTC patients rapidly increased due to lymph node metastases or distant metastasis. Therefore, it needs to distill an enhanced understanding of the pathogenesis of PTC patients with lymph node metastases or distant metastasis. We employed the TMT-based quantitative proteomics approach to identify and analyze differentially expressed proteins in PTC with different degrees of lymph node metastases. Compared with paired normal tissues, asporin is overexpressed in PTC-N0, PTC-N1a, and PTC-N1b tumorous tissues via proteomics, western blotting, and immunohistochemistry assays. Functionally, asporin is mainly expressed in the extracellular matrix, cell membrane, and cytoplasm of PTC tumorous tissues, and promotes thyroid cancer cell proliferation, migration, and invasion. Mechanistically, asporin, interacting with HER2, co-localizes HER2 on the cell membrane and cytoplasm, and the asporin/HER2/SRC/EGFR axis upregulate the expression of EMT-activating transcription factors through the MAPK signaling pathway. Clinically, asporin can be regarded as a serological biomarker to identify PTC patients with or without lymph node metastasis, and high expression of asporin in PTC tumorous tissues is a risk factor for poor prognosis.
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影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
4.6
作者：
Dai YJ;Qiu YB;Jiang R;Xu M;Zhao L;Chen GG;Liu ZM
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Liu ZM
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作者：
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Ikegawa, S
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21.3
作者：
Kajiro, Masashi;Hirota, Ryuichi;Yanagisawa, Junn
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Yanagisawa, Junn
影响因子：
4.8
作者：
Biscardi, JS;Maa, MC;Parsons, SJ
通讯作者：
Parsons, SJ