Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
Department of Radiology, University of California, San Diego, The, USA.
J Transl Med. 2024 Jun 6;22(1):537. doi: 10.1186/s12967-024-05324-2.
Accumulating evidence indicated that HHEX participated in the initiation and development of several cancers, but the potential roles and mechanisms of HHEX in hepatocellular carcinoma (HCC) were largely unclear. Cancer stem cells (CSCs) are responsible for cancer progression owing to their stemness characteristics. We reported that HHEX was a novel CSCs target for HCC. We found that HHEX was overexpressed in HCC tissues and high expression of HHEX was associated with poor survival. Subsequently, we found that HHEX promoted HCC cell proliferation, migration, and invasion. Moreover, bioinformatics analysis and experiments verified that HHEX promoted stem cell-like properties in HCC. Mechanistically, ABI2 serving as a co-activator of transcriptional factor HHEX upregulated SLC17A9 to promote HCC cancer stem cell-like properties and tumorigenesis. Collectively, the HHEX-mediated ABI2/SLC17A9 axis contributes to HCC growth and metastasis by maintaining the CSC population, suggesting that HHEX serves as a promising therapeutic target for HCC treatment.
越来越多的证据表明 HHEX 参与了多种癌症的发生和发展，但 HHEX 在肝细胞癌（HCC）中的潜在作用和机制在很大程度上尚不清楚。癌症干细胞（CSCs）由于其干细胞特性而负责癌症的进展。我们报道 HHEX 是 HCC 的新型 CSCs 靶标。我们发现 HHEX 在 HCC 组织中过表达，HHEX 的高表达与不良预后相关。随后，我们发现 HHEX 促进 HCC 细胞的增殖、迁移和侵袭。此外，生物信息学分析和实验验证了 HHEX 促进 HCC 中的干细胞样特性。在机制上，ABI2 作为转录因子 HHEX 的共激活因子，上调 SLC17A9 以促进 HCC 癌干细胞样特性和肿瘤发生。总之，HHEX 介导的 ABI2/SLC17A9 轴通过维持 CSC 群体促进 HCC 的生长和转移，表明 HHEX 可作为 HCC 治疗的有前途的治疗靶点。
