MC1R信号通过cAMP-CREB/ATF-1和ERK-NFκB途径加速G1/S转变，促进乳腺癌进展。
MC1R signaling through the cAMP-CREB/ATF-1 and ERK-NFκB pathways accelerates G1/S transition promoting breast cancer progression.
发表日期：2023 Sep 07
作者：
Vipin Shankar Chelakkot, Kiara Thomas, Todd Romigh, Andrew Fong, Lin Li, Shira Ronen, Shuyang Chen, Pauline Funchain, Ying Ni, Joshua Arbesman
来源：
npj Precision Oncology
摘要：
MC1R，一个G蛋白偶联受体，能够在黑色素细胞中触发紫外线诱导的黑色素合成和DNA修复，并与黑色素瘤的发病机制相关。虽然MC1R广泛在不同组织类型中表达，但其在非皮肤组织中的功能相对未知。在本研究中，我们展示了与黑色素瘤发生相关的MC1R变异在多种癌症患者中较少被发现。进一步的探索表明，与正常乳腺组织相比，乳腺癌组织中MC1R的表达显著增加，且MC1R的沉默显著降低了乳腺癌细胞的体外和体内增殖。机制上，MC1R信号通过MC1R-cAMP-CREB/ATF-1和MC1R-ERK-NFκB轴加速了乳腺癌细胞的G1-S转变。我们的结果揭示了MC1R与乳腺癌之间的新关联，这可能在治疗上具有潜在的靶向性。此外，我们的结果表明，在特定环境中，MC1R增强/激活疗法应谨慎使用，因为它们可能在某些情况下促进肿瘤发展。© 2023. Nature Publishing Group UK.
MC1R, a G-protein coupled receptor, triggers ultraviolet light-induced melanin synthesis and DNA repair in melanocytes and is implicated in the pathogenesis of melanoma. Although widely expressed in different tissue types, its function in non-cutaneous tissue is relatively unknown. Herein, we demonstrate that disruptive MC1R variants associated with melanomagenesis are less frequently found in patients with several cancers. Further exploration revealed that breast cancer tissue shows a significantly higher MC1R expression than normal breast tissue, and knocking down MC1R significantly reduced cell proliferation in vitro and in vivo. Mechanistically, MC1R signaling through the MC1R-cAMP-CREB/ATF-1 and MC1R-ERK-NFκB axes accelerated the G1-S transition in breast cancer cells. Our results revealed a new association between MC1R and breast cancer, which could be potentially targeted therapeutically. Moreover, our results suggest that MC1R-enhancing/activating therapies should be used cautiously, as they might be pro-tumorigenic in certain contexts.© 2023. Nature Publishing Group UK.