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.

磷酸赖氨酸磷酸组氨酸无机焦磷酸磷酸酶（LHPP）是一种组氨酸磷酸酶，作为肿瘤抑制因子在肿瘤进展和转移中发挥重要作用。在这里，我们研究 LHPP 在肝内胆管癌 (ICC) 中的作用。我们发现 LHPP 在肿瘤组织中下调，低水平的 LHPP 预示着较差的生存率。 LHPP在体外和体内抑制 ICC 细胞生长、细胞侵袭和上皮间质转化 (EMT)。从机制上讲，LHPP 使转化生长因子 β (TGFβ) 信号通路失活，低水平的 LHPP 上调 TGFβ 的表达和 smad2/3 的磷酸化。此外，抑制该途径会逆转 LHPP 的生物功能。总之，这些研究结果表明，LHPP 通过抑制 TGFβ/smad 信号传导的激活来抑制 ICC。我们的结果表明 LHPP 是 ICC 的潜在治疗靶点。