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

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.

Automated summary

Cancer cells modulate metabolic activities in order to adapt to their growth and proliferation. This study investigates the role of the enzyme SHMT2 in breast cancer and its potential as a therapeutic target. The researchers found that SHMT2 was highly expressed in breast cancer cells and tissues, and patients with high SHMT2 expression had worse prognosis. In vitro experiments showed that manipulating SHMT2 affected breast cancer cell proliferation. RNA-seq analysis revealed that SHMT2 over-expression influenced multiple signaling pathways and biological processes. Further investigation confirmed that SHMT2 promotes breast cancer growth through the MAPK and VEGF signaling pathways.