Xie Shuang-Yan, Shi Ding-Bo, Ouyang Yi, Lin Fei, Chen Xiao-Yu, Jiang Tong-Chao, Xia Wen, Guo Ling, Lin Huan-Xin
Department of Radiotherapy, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Collaborative Innovation Center for Cancer Medicine 651 Dongfeng Road East, Guangzhou 510060, Guangdong, China.
Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou, Guangdong, China.
Am J Cancer Res. 2022 Jul 15;12(7):3405-3421. eCollection 2022.
Cancer cells modulate their metabolic activities to adapt to their growth and proliferation. Despite advances in breast cancer biology having led to the widespread use of molecular targeted therapy and hormonal drugs, the molecular mechanisms in metabolism related to the regulation of breast cancer cell proliferation are still poorly understood. Here, we investigate the possible role of SHMT2, a key enzyme in serine metabolism, in breast cancer. Firstly, SHMT2 is found highly expressed in both breast cancer cells and tissues, and patients with high expression of SHMT2 have a worse prognosis. Moreover, the intervention of SHMT2 by either knockdown or over-expression in vitro induces the effect on breast cancer proliferation. Mechanistically, RNA-seq shows that over-expression of SHMT2 affect multiple signaling pathways and biological process in breast cancer cells. Furthermore, we confirm that SHMT2 promotes breast cancer cell growth through MAPK and VEGF signaling pathways. Finally, we verify the role of SHMT2 in promoting breast cancer growth in the xenograft tumor model. Our results indicate that SHMT2 plays a critical role in regulating breast cancer growth through MAPK, and VEGF signaling pathways, and maybe serve as a therapeutic target for breast cancer therapy.
癌细胞调节其代谢活动以适应其生长和增殖。尽管乳腺癌生物学的进展已导致分子靶向治疗和激素药物的广泛应用，但与乳腺癌细胞增殖调节相关的代谢分子机制仍知之甚少。在此，我们研究丝氨酸代谢中的关键酶SHMT2在乳腺癌中的可能作用。首先，发现SHMT2在乳腺癌细胞和组织中均高度表达，且SHMT2高表达的患者预后较差。此外，在体外通过敲低或过表达对SHMT2进行干预可诱导对乳腺癌增殖的影响。从机制上讲，RNA测序表明SHMT2的过表达影响乳腺癌细胞中的多个信号通路和生物学过程。此外，我们证实SHMT2通过MAPK和VEGF信号通路促进乳腺癌细胞生长。最后，我们在异种移植肿瘤模型中验证了SHMT2在促进乳腺癌生长中的作用。我们的结果表明，SHMT2通过MAPK和VEGF信号通路在调节乳腺癌生长中起关键作用，并且可能作为乳腺癌治疗的治疗靶点。
