1. Academic Validation
  2. SHMT2 promotes tumor growth through VEGF and MAPK signaling pathway in breast cancer

SHMT2 promotes tumor growth through VEGF and MAPK signaling pathway in breast cancer

  • Am J Cancer Res. 2022 Jul 15;12(7):3405-3421.
Shuang-Yan Xie 1 2 Ding-Bo Shi 3 Yi Ouyang 1 Fei Lin 1 Xiao-Yu Chen 1 Tong-Chao Jiang 1 Wen Xia 1 Ling Guo 4 Huan-Xin Lin 1
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou, Guangdong, China.
  • 3 Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, Guangdong, China.
  • 4 Department of Nasopharyngeal Carcinoma, 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.
PMID: 35968337
Abstract

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.

Keywords

MAPK; SHMT2; VEGF; breast cancer; serine/glycine metabolism.

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