The adipokine chemerin has been considered an important regulator of tumor immune surveillance. Chemerin recruits leukocytes through the receptor CMKLR1 to improve clinical outcomes of tumors and overall patient survival, but the role of GPR1 in tumors has not been widely investigated. Here, we found that GPR1 expression is elevated in breast cancer—especially triple-negative breast cancer (TNBC) tissues and cell lines. Herein, we screened a phage display peptide library to identify LRH7-G5, a peptide antagonist that blocks chemerin/GPR1 signaling. This peptide performed as an anticancer agent to suppress the proliferation of the TNBC cell lines MDA-MB-231 and HCC1937 but has little effect on T47D cells. LRH7-G5 treatment significantly blocked tumor growth in a TNBC cell-bearing orthotopic mouse model. Last, our results showed that this peptide’s antitumor role is mediated through the PI3K/AKT signaling pathway. In conclusion, these data collectively suggest that the chemerin receptor GPR1 is a novel target for controlling TNBC progression and establish peptide LRH7-G5 as a new therapeutic agent for suppressing TNBC tumor growth.

己几丁质凯莫瑞被认为是肿瘤免疫监视的重要调节剂。Chemerin通过受体CMKLR1募集白细胞以改善肿瘤的临床结局和总体患者生存率，但是GPR1在肿瘤中的作用尚未得到广泛研究。在这里，我们发现GPR1表达在乳腺癌（尤其是三阴性乳腺癌（TNBC）组织和细胞系）中升高。在本文中，我们筛选了噬菌体展示肽库以鉴定LRH7-G5，这是一种阻断chemerin / GPR1信号传导的肽拮抗剂。该肽作为抗癌剂来抑制TNBC细胞系MDA-MB-231和HCC1937的增殖，但对T47D细胞影响很小。LRH7-G5处理在带有TNBC细胞的原位小鼠模型中显着阻断了肿瘤的生长。持续，我们的结果表明，该肽的抗肿瘤作用是通过PI3K / AKT信号传导途径介导的。总之，这些数据共同表明，凯莫瑞受体GPR1是控制TNBC进程的新靶标，并确立了肽LRH7-G5作为抑制TNBC肿瘤生长的新治疗剂。