Kong Yanan, Ou Xueqi, Li Xing, Zeng Yan, Gao Guanfeng, Lyu Ning, Liu Peng
Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 East Dongfeng Road, Guangzhou 510060, China.
Department of Minimally Invasive Interventional Radiology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 East Dongfeng Road, Guangzhou 510060, China.
Mol Ther Oncolytics. 2020 Jun 24;18:351-359. doi: 10.1016/j.omto.2020.06.020. eCollection 2020 Sep 25.
Leucine-rich-repeat-containing G protein-coupled receptor 6 (LGR6) has been identified as the stem cell marker in multiple normal tissues and malignancies. Previous studies implicated paradoxical functions of LGR6 as a tumor-suppressor gene or oncogene given to the specific context. To explore the exact role of LGR6 in triple-negative breast cancer (TNBC) that never has been studied before, in this study, we assessed LGR6 expression levels by RT-PCR and immunohistochemistry. LGR6 stable expressing/silenced cells were established, and functional assays on tumor proliferation, as well as metastasis, were conducted both and . Here, we found that LGR6 was overexpressed in TNBC, which correlated with poor disease-free and overall survivals. Functional assays both and showed that LGR6 promotes tumor proliferation and metastasis. LGR6 also increased the ability of tumor spheroid formation. Underlying mechanism exploration further revealed that the oncogenic role of LGR6 might be associated with the Wnt/β-catenin pathway. In conclusion, our findings first proved that LGR6 acts as an oncogene in (TNBC), indicating that LGR6 might be a potential therapeutic target for TNBC treatment.
富含亮氨酸重复序列的G蛋白偶联受体6（LGR6）已被确定为多种正常组织和恶性肿瘤中的干细胞标志物。先前的研究表明，鉴于特定背景，LGR6具有作为肿瘤抑制基因或癌基因的矛盾功能。为了探索LGR6在从未被研究过的三阴性乳腺癌（TNBC）中的确切作用，在本研究中，我们通过RT-PCR和免疫组织化学评估了LGR6的表达水平。建立了LGR6稳定表达/沉默细胞，并在体内和体外进行了肿瘤增殖以及转移的功能测定。在此，我们发现LGR6在TNBC中过表达，这与无病生存期和总生存期较差相关。体内和体外功能测定均表明LGR6促进肿瘤增殖和转移。LGR6还增加了肿瘤球形成的能力。潜在机制探索进一步揭示，LGR6的致癌作用可能与Wnt/β-连环蛋白通路有关。总之，我们的研究结果首次证明LGR6在（TNBC）中作为癌基因起作用，表明LGR6可能是TNBC治疗的潜在治疗靶点。
