LHPP suppresses tumorigenesis of intrahepatic cholangiocarcinoma by inhibiting the TGFβ/smad signaling pathway

Our results demonstrated that LHPP suppressed ICC tumorigenesis through inhibiting the TGFβ/smad signaling pathway. [Display omitted] •LHPP was downregulated in ICC and predicted poor survival.•As a tumor suppressor, LHPP inhibited ICC cell growth, cell invasion and EMT in vitro and in vivo.•LHPP suppressed ICC by inhibiting TGFβ/smad signaling pathway. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP), a histidine phosphatase, plays an important role in tumor progression and metastasis as a tumor suppressor. Here, we investigate the effect of LHPP in intrahepatic cholangiocarcinoma (ICC). We discovered that LHPP was downregulated in tumor tissues and low levels of LHPP predicted poor survival. LHPP inhibited ICC cell growth, cell invasion and epithelial–mesenchymal transition (EMT) in vitro and in vivo. Mechanically, LHPP deactivated transforming growth factor‑beta (TGFβ) signaling pathway, and low level LHPP upregulated the expression of TGFβ and phosphorylation of smad2/3. Moreover, inhibition of this pathway reversed the biofunction of LHPP. In summary, these findings demonstrated that LHPP suppressed ICC through inhibiting the activation of TGFβ/smad signaling. Our results indicated that LHPP is a potential therapeutic target in ICC.