肝细胞癌（HCC）是最常见的原发性肝癌类型，以其侵袭性行为和不良预后而闻名。癌症干细胞理论假设存在一小群称为癌症干细胞 (CSC) 的自我更新细胞，该理论提供了对 HCC 各种临床和分子特征的见解，例如肿瘤异质性、代谢适应性、治疗耐药性和复发。这些 CSC 在肿瘤微环境 (TME) 中培育，内部和外部因素的混合创造了一个在空间和时间上不断进化的肿瘤支持生态位，从而增强了肿瘤的复杂性。这篇综述详细介绍了肝脏 CSC (HCSC) 的起源以及影响其干细胞特性的因素。它强调了 HCSC 和 TME（缺氧、血管、侵袭和免疫生态位）之间的相互串扰，探索所涉及的信号通路以及这些相互作用如何控制 CSC 的恶性特征。此外，它还讨论了针对 HCSC 利基的潜在治疗方法及其在临床实践中的可能用途。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Hepatocellular Carcinoma (HCC), the most prevalent type of primary liver cancer, is known for its aggressive behavior and poor prognosis. The Cancer Stem Cell theory, which postulates the presence of a small population of self-renewing cells called Cancer Stem Cells (CSCs), provides insights into various clinical and molecular features of HCC such as tumor heterogeneity, metabolic adaptability, therapy resistance, and recurrence. These CSCs are nurtured in the tumor microenvironment (TME), where a mix of internal and external factors creates a tumor-supportive niche that is continuously evolving both spatially and temporally, thus enhancing the tumor's complexity. This review details the origins of hepatic CSCs (HCSCs) and the factors influencing their stem-like qualities. It highlights the reciprocal crosstalk between HCSCs and the TME (hypoxic, vascular, invasive, and immune niches), exploring the signaling pathways involved and how these interactions control the malignant traits of CSCs. Additionally, it discusses potential therapeutic approaches targeting the HCSC niche and their possible uses in clinical practice.Copyright © 2024 Elsevier Ltd. All rights reserved.