PRMT1 Regulates EGFR and Wnt Signaling Pathways and Is a Promising Target for Combinatorial Treatment of Breast Cancer.
PRMT1 Regulates EGFR and Wnt Signaling Pathways and Is a Promising Target for Combinatorial Treatment of Breast Cancer.
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DOI：
10.3390/cancers14020306
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发表时间：
2022-01-08
期刊：
影响因子：
5.2
通讯作者：
Dubois T
中科院分区：
文献类型：
--
作者：
Suresh S;Huard S;Brisson A;Némati F;Dakroub R;Poulard C;Ye M;Martel E;Reyes C;Silvestre DC;Meseure D;Nicolas A;Gentien D;Fayyad-Kazan H;Le Romancer M;Decaudin D;Roman-Roman S;Dubois T
三阴性乳腺癌（TNBC）患者最初对化疗反应良好，但容易复发。在寻找新的治疗靶点时，我们发现PRMT1在TNBC肿瘤样本中高表达，对乳腺癌细胞存活至关重要。此外，本研究提出靶向PRMT1联合化疗可以改善TNBC患者的生存结果。为三阴性乳腺癌（TNBC）患者确定新的治疗策略是一个优先事项，因为这些患者在化疗后极易复发。在这里，我们发现蛋白精氨酸甲基转移酶1 （PRMT1）在所有乳腺癌亚型中高度表达。在各种乳腺癌细胞系中，PRMT1缺失通过诱导DNA损伤和凋亡降低细胞存活。转录组学分析和染色质免疫沉淀显示，PRMT1调节表皮生长因子受体（EGFR）和Wnt信号通路，据报道在TNBC中被激活。PRMT1酶活性也需要刺激典型的Wnt途径。在TNBC异种移植模型中，I型PRMT抑制剂可降低乳腺癌细胞增殖并显示抗肿瘤活性。这些抑制剂与一些用于治疗TNBC患者的化疗药物以及EGFR抑制剂厄洛替尼显示出协同相互作用。因此，靶向PRMT1联合这些化疗可能会改善TNBC患者的现有治疗方法。
Patients with triple-negative breast cancer (TNBC) respond well to chemotherapy initially but are prone to relapse. Searching for new therapeutic targets, we found that PRMT1 is highly expressed in TNBC tumor samples and is essential for breast cancer cell survival. Furthermore, this study proposes that targeting PRMT1 in combination with chemotherapies could improve the survival outcome of TNBC patients. Identifying new therapeutic strategies for triple-negative breast cancer (TNBC) patients is a priority as these patients are highly prone to relapse after chemotherapy. Here, we found that protein arginine methyltransferase 1 (PRMT1) is highly expressed in all breast cancer subtypes. PRMT1 depletion decreases cell survival by inducing DNA damage and apoptosis in various breast cancer cell lines. Transcriptomic analysis and chromatin immunoprecipitation revealed that PRMT1 regulates the epidermal growth factor receptor (EGFR) and the Wnt signaling pathways, reported to be activated in TNBC. PRMT1 enzymatic activity is also required to stimulate the canonical Wnt pathway. Type I PRMT inhibitors decrease breast cancer cell proliferation and show anti-tumor activity in a TNBC xenograft model. These inhibitors display synergistic interactions with some chemotherapies used to treat TNBC patients as well as erlotinib, an EGFR inhibitor. Therefore, targeting PRMT1 in combination with these chemotherapies may improve existing treatments for TNBC patients.
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影响因子：
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作者：
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通讯作者：
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