Kallikrein-related peptidase (KLK10) cessation blunts colorectal cancer cell growth and glucose metabolism by regulating the PI3K/Akt/mTOR pathway.

Colorectal cancer (CRC) is a common aggressive carcinoma with a proverbial feature of metabolic reprogramming that is essential for cancer cell growth. Recent research corroborates the controversial function of kallikrein-related peptidase 10 (KLK10) in cancer. However, its role and underlying mechanism in CRC remains elusive. In the present study, high expression of KLK10 was detected in CRC cell lines. Knockdown of KLK10 expression by a specific siRNA inhibited cell proliferation, evoked cell apoptosis, and increased caspase-3 activity in HT29 CRC cells. Furthermore, KLK10 suppression also afforded the suppressive effects on glycolysis in CRC cells as the data showed that targeting KLK10 restrained glucose uptake, lactate production, and glycolysis-related glucose transporter 1 (Glut1) expression. Mechanism analysis corroborated that cessation of KLK10 muted the PI3K/AKT-mTOR signaling. Intriguingly, reactivating the PI3K/AKT-mTOR pathway by its agonist IGF-1 notably reversed the inhibitory effects of KLK10 cessation on CRC cell growth and glucose metabolism. More important, preconditioning with PI3K/AKT inhibitor LY294002 or mTOR inhibitor rapamycin both aggravated KLK10 knockdown-suppressed cancer cell growth and glucose metabolism. These findings suggest that KLK10 silencing may attenuate the progression of CRC by inhibiting cell growth and glycolysis via the PI3K/AKT/mTOR signaling, supporting a potential and promising target for CRC therapy.

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