KIAA1114, a full-length protein encoded by the trophinin gene, is a novel surface marker for isolating tumor-initiating cells of multiple hepatocellular carcinoma subtypes

Abstract

Identification of novel biomarkers for tumor-initiating cells (TICs) is of critical importance for developing diagnostic and therapeutic strategies against cancers. Here we identified the role of KIAA1114, a full-length translational product of the trophinin gene, as a distinctive marker for TICs in human liver cancer by developing a DNA vaccine-induced monoclonal antibody targeting the putative extracellular domain of KIAA1114. Compared with other established markers of liver TICs, KIAA1114 was unique in that its expression was detected in both alpha fetoprotein (AFP)-positive and AFP-negative hepatocellular carcinoma (HCC) cell lines with the expression levels of KIAA1114 being positively correlated to their tumorigenic potentials. Notably, KIAA1114 expression was strongly detected in primary hepatic tumor, but neither in the adjacent non-tumorous tissue from the same patient nor normal liver tissue. KIAA1114high cells isolated from HCC cell lines displayed TIC-like features with superior functional and phenotypic traits compared to their KIAA1114low counterparts, including tumorigenic abilities in xenotransplantation model, in vitro colony- and spheroid-forming capabilities, expression of stemness-associated genes, and migratory capacity. Our findings not only address the value of a novel antigen, KIAA1114, as a potential diagnostic factor of human liver cancer, but also as an independent biomarker for identifying TIC populations that could be broadly applied to the heterogeneous HCC subtypes.

miR-1236 down-regulates alpha-fetoprotein, thus causing PTEN accumulation, which inhibits the PI3K/Akt pathway and malignant phenotype in hepatoma cells

“…It was reported that AFP, KIF18A and KIAA1114 are biological markers correlated with HCC [30, 31], and AFP is widely used in clinical. The re-expression of AFP in most HCC patients has been studied for decades.…”

Embryo–epithelium interactions during implantation at a glance

“…Trophinin is one of three membrane proteins derived from the TRO gene (also known as MAGE-D3) (Kim et al, 2014) and mediates Ca 2+ -independent homophilic cell adhesion in synergy with its cytoplasmic partners tastin (also known as TROAP), bystin and ErbB4 (Fukuda and Sugihara, 2012;see poster). Binding of trophinin from an adjacent cell is predicted to dissociate bystin, thereby permitting phosphorylation of ErbB4 when heparin-binding epidermal-like growth factor (HB-EGF) is bound to ErbB4 (Sugihara et al, 2007).…”

MCM family in HCC: MCM6 indicates adverse tumor features and poor outcomes and promotes S/G2 cell cycle progression

“…The comparison among MCMs in HCC has not yet been performed. Hepatocarcinogenesis is a typical multistage process characterized by chronic viral infection, cirrhosis, and HCC [ 28 , 29 ]. Here, we feature the expression dynamics of MCM2, MCM3, MCM4, MCM5, MCM6, MCM7, MCM8, MCM9, MCM10 and RecQ like helicase 4 (RECQL4) in the typical multistep of hepatocarcinogenesis and demonstrate the association between MCMs and clinicopathological characteristics, diagnosis and prognosis in HCC patients.…”