Cell division cycle 20 (CDC20) is frequently overexpressed in malignant tumours and involved in the differentiation process of hematopoietic stem cells. However, the role of CDC20 in prostate cancer stem-like cells (CSCs) remains poorly understood. The expression of CDC20, CD44, β-catenin were examined in prostate cancer specimens by immunohistochemistry assay, the role of CDC20 on the stem-like properties of prostate CSCs was accessed by real-time quantitive PCR, spheroid formation, in vitro and in vivo limiting dilution assay. CDC20 was associated with malignant progression of prostate cancer, the patients with both high expression CDC20 and CD44 or β-catenin were associated with more aggressive clinicopathological features and poor prognosis. CDC20 was usually enriched in CD44+ prostate CSCs. Knockdown of CDC20 could inhibit the expression of stemness-related genes, self-renewal ability, chemo-resistance, invasion capability and tumorigenicity of CD44+ prostate CSCs. Mechanistically, CDC20 promoted degradation of Axin1, the core member of β-catenin destruction complex, sequentially reduced the phosphorylation of β-catenin, promoting the latter into the nucleus, thereby enhancing the self-renewal capacity of CD44+ prostate CSCs. Our results indicated that CDC20 maintains the self-renewal ability of CD44+ prostate CSCs by promoting nuclear translocation and trans-activation of β-catenin. In addition, CDC20 combined with CD44 or β-catenin can serve as an important indicator for prognosis of patients with prostate cancer.

CD146 plays a key role in cancer progression and metastasis. Cancer stem cells (CSCs) are responsible for tumor initiation, drug resistance, metastasis, and recurrence. In this study, we explored the role of CD146 in the regulation of liver CSCs. Here, we demonstrated that CD146 was highly expressed in liver CSCs. CD146 overexpression promoted the self-renewal ability and chemoresistance of Hepatocellular Carcinoma (HCC) cells in vitro and tumorigenicity in vivo. Inversely, knockdown of CD146 restrained these abilities. Mechanistically, CD146 activated the NF-κB signaling to up-regulate JAG2 expression and activated the Notch signaling, which resulted in increased stemness of HCC. Furthermore, JAG2 overexpression restored the Notch signaling activity, the stemness, and chemotherapeutic resistance caused by CD146 knockdown. These results demonstrated that CD146 positively regulates HCC stemness by activating the JAG2-NOTCH signaling. Combined targeting of CD146 and JAG2 may represent a novel therapeutic strategy for HCC treatment.

BACKGROUND Metabolic dysregulation is considered a significant hallmark of hepatocellular carcinoma (HCC). SAC3 domain containing 1 (SAC3D1) functions in the cell cycle, and its expression is upregulated in various cancers. It is known that metabolic changes occur at different stages of the cell cycle to maintain the biosynthesis and replication of both normal and cancer cells. Based on the role of SAC3D1 in mitosis, we hypothesize that abnormal expression of SAC3D1 may affect cellular metabolism. However, it remains unclear whether SAC3D1 mediates the progression of HCC by regulating metabolic reprogramming. AIM To comprehensively elucidate the impact and molecular mechanism of SAC3D1 on the progression of HCC by regulating the metabolic reprogramming. METHODS The constructed SAC3D1 overexpression and knockdown HCC cell lines were used for detecting cell proliferation, migration capabilities, as well as glycolysis and adenosine triphosphate (ATP) production rate assays. They were also employed for examining molecular markers associated with cell migration and glycolysis. The transcriptome sequencing data of cells have revealed the pathways potentially influenced by SAC3D1.The tail vein metastasis model and xenograft tumor experiments were utilized to demonstrate SAC3D1’s tumor-promoting effects in vivo . RESULTS SAC3D1 expression was upregulated and associated with poor prognosis in HCC patients. SAC3D1 enhanced the proliferation and migration abilities and reduced the population dependence of HCC cells in vitro and in vivo . The upregulation of SAC3D1 enhanced cellular glycolysis and ATP production. The cell transcriptome sequencing data revealed that SAC3D1 activated Wnt signaling pathway. SAC3D1 did not modulate the transcription of β-Catenin , while might inhibit its degradation. Further investigations indicated that the increase of SAC3D1 leads to more β-Catenin accumulating in the nucleus, facilitating the expression of c-Myc, one of the upstream regulatory factors of glycolysis. The iCRT3, an antagonist of β-Catenin, could counteract the increase of c-Myc induced by SAC3D1, while also downregulating the expression of glycolysis-related proteins. CONCLUSION This study found that SAC3D1 enhances HCC cell glycolysis and ATP production via the β-Catenin/c-Myc signaling axis, thereby promoting the progression of HCC.

Extracellular vesicles (EVs) can deliver many types of drugs with their natural source material transport properties, inherent long-term blood circulation capabilities and excellent biocompatibility, and have great potential in the field of drug carrier. Modification of the content and surface of EVs according to the purpose of treatment has become a research focus to improve the drug load and the targeting of EVs. EVs can maximize the stability of the drugs, prevent immune clearance and achieve accurate delivery. Therefore, EVs can be described as \" stealth transport aircrafts \" for drugs. This chapter will respectively introduce the application of natural EVs as cell substitutes in cell therapy and engineered EVs as carriers of nucleic acids, proteins, small molecule drugs and therapeutic viral particles in disease treatment. It will also explain the drug loading and modification strategies of EVs, the source and characteristics of EVs. In addition, the commercialization progress of EVs drugs will be mentioned here, and the problems in their applications will be discussed in conjunction with the application of EVs in the treatment of COVID-19.