Background: Iron metabolism is essential because it plays regulatory roles in various physiological and pathological processes. Disorders of iron metabolism balance are related to various cancers, including hepatocellular carcinoma. Cancer stem-like cells (CSCs) exert critical effects on chemotherapy failure, cancer metastasis, and subsequent disease recurrence and relapse. However, little is known about how iron metabolism affects liver CSCs. Here, we investigated the expression of transferrin receptor 1 (TFR1) and ferroportin (FPN), two iron importers, and an upstream regulator, iron regulatory protein 2 (IRP2), in liver hepatocellular carcinoma (LIHC) and related CSCs.Methods: The expression levels of TFR1, FPN and IRP2 were analysed using the GEPIA database. CSCs were derived from parental LIHC cells cultured in serum-free medium. After TFR1 knockdown, ROS accumulation and malignant behaviours were measured. The CCK-8 assay was performed to detect cell viability after TFR1 knockdown and erastin treatment.Results: TFR1 expression was upregulated in LIHC tissue and CSCs derived from LIHC cell lines, prompting us to investigate the roles of TFR1 in regulating CSCs. Knockdown of TFR1 expression decreased iron accumulation and inhibited malignant behaviour. Knockdown of TFR1 expression decreased reactive oxygen species (ROS) accumulation induced by erastin treatment and maintained mitochondrial function, indicating that TFR1 is critical in regulating erastin-induced cell death in CSCs. Additionally, knockdown of TFR1 expression decreased sphere formation by decreasing iron accumulation in CSCs, indicating a potential role for TFR1 in maintaining stemness.Conclusion: These findings, which revealed TFR1 as a critical regulator of LIHC CSCs in malignant behaviour and stemness that functions by regulating iron accumulation, may have implications to improve therapeutic approaches.

Colorectal cancer (CRC) is a common cancer worldwide with poor prognosis. The presence of Fusobacterium nucleatum (Fn) in the intestinal mucosa is associated with the progression of CRC. In this review, we explore the mechanisms by which Fn contributes to proliferation and migration of CRC cells from the following four aspects: induction of the epithelial–mesenchymal transition (EMT), regulation of the tumor microenvironment (TME), expression of oncogenic noncoding RNAs, and DNA damage. This review outlines the scientific basis for the use of Fn as a biomarker and therapeutic target in CRC.

Anlotinib is a multi‐target tyrosine kinase inhibitor. Previous studies confirmed that anlotinib exerts anti‐cancer efficiency. However, the functional roles of anlotinib on cancer stem cells (CSCs) are yet to be elucidated. In this study, lung CSCs were isolated and identified in vitro, and mouse xenografts were established in vivo. MTT assays, tumour sphere formation assays, TdT‐mediated dUTP nick‐end labelling (TUNEL) staining, Annexin V‐FITC/PI staining, immunofluorescence analysis and Western blot were performed to investigate the anti‐cancer effects of anlotinib on lung CSCs. The results showed that anlotinib inhibits the growth of lung CSCs in vitro and in vivo. In addition, anlotinib induced apoptosis of these cells along with down‐regulated expression level of Bcl‐2 whereas up‐regulated Bax and cleaved caspase‐3 expression. It also sensitized lung CSCs to the cytotoxicity of cisplatin and paclitaxel; the tumour sphere formation and expression levels of multiple stemness‐associated markers, such as ALDH1 and CD133, were also decreased. Furthermore, the underlying mechanism indicated that anlotinib reduces the phosphorylated levels of NF‐κB p65 and IκB‐α in lung CSCs. Taken together, these findings suggested that anlotinib exerts potent anti‐cancer effects against lung CSCs through apoptotic induction and stemness phenotypic attenuation. The mechanism could be associated with the suppression of NF‐κB activity.