Kisspeptin 10 inhibits the Warburg effect in breast cancer through the Smad signaling pathway: both in vitro and in vivo.

Breast cancer is the most frequently diagnosed cancer in females. Warburg effect could enhance tumorigenesis and has garnered attention as a target for tumor treatment. In this study, we found that the mRNA and protein levels of hexokinase 2 (HK2), pyruvate kinase (PKM2), and pyruvate dehydrogenase kinase (PDK1) in breast cancer tissues were higher than those in corresponding noncancerous tissues. HK2, PKM2, and PDK1 expression was correlated statistically with the survival rate of the patients with breast cancer. We also demonstrated a shorter fragment of KISS1, Kisspeptin-10 (KP-10), inhibited the Warburg effect and induced mitochondrial injury in human breast cancer cell line, MDA-MB-231. We confirmed that KP-10-inhibited the Warburg effect by activating Smad pathway. The effects and related mechanisms of these treatments were also confirmed in murine xenografts. However, additional studies are needed to confirm these results in other cell types.