Sphingosine-1-phosphate transporter spinster homolog 2 is essential for iron-regulated metastasis of hepatocellular carcinoma.

ABSTRACT: Iron dyshomeostasis is associated with hepatocellular carcinoma (HCC) development. However, the role of iron in HCC metastasis is unknown. This study aimed to elucidate the underlying mechanisms of iron's enhancement activity on HCC metastasis. In addition to the HCC cell lines and clinical samples in vitro, iron-deficient (ID) mouse models were generated using iron-free diet and transferrin receptor protein knockout, followed by administration of HCC tumors through either orthotopic or ectopic route. Clinical metastatic HCC samples showed significant ID status, accompanied by overexpression of sphingosine-1-phosphate transporter spinster homolog 2 (SPNS2). Mechanistically, ID increased SPNS2 expression, leading to HCC metastasis in both cell cultures and mouse models. ID not only altered

SUBMITTER: Li M 

PROVIDER: S-EPMC8821935 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature