Display omitted
•WNT/β-catenin signaling plays a role in the progress of HCC.•WNT signaling plays a role in the progress of Cholangiocarcinoma.•Targeting WNT ligands and FZD protein to treat liver ...cancer.•Targeting Porcupine and DKK1 to treat liver cancer.
The WNT/β-catenin signaling pathway is a highly conserved and tightly controlled molecular mechanism that regulates embryonic development, cellular proliferation and differentiation. Of note, accumulating evidence has shown that the aberrant of WNT/β-catenin signaling promotes the development and/or progression of liver cancer, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the two most prevalent primary liver tumours in adults. There are two different WNT signaling pathways have been identified, which were termed non-canonical and canonical pathways, the latter involving the activation of β-catenin. β-catenin, acting as an intracellular signal transducer in the WNT signaling pathway, is encoded by CTNNB1 and plays a critical role in tumorigenesis. In the past research, most liver tumors have mutations in genes encoding key components of the WNT/β-catenin signaling pathway. In addition, several of other signaling pathways also can crosswalk with β-catenin. In this review, we discuss the most relevant molecular mechanisms of action and regulation of WNT/β-catenin signaling in the development and pathophysiology of liver cancers, as well as in the development of therapeutics.
Hypoxia is a remarkable trait of the tumor microenvironment (TME). When facing selective pressure, tumor cells show various adaptive characteristics, such as changes in the expression of cancer ...hallmarks (increased proliferation, suppressed apoptosis, immune evasion, and so on) and more frequent cell communication. Because of the adaptation of cancer cells to hypoxia, exploring the association between cell communication mediators and hypoxia has become increasingly important. Exosomes are important information carriers in cell-to-cell communication. Abundant evidence has proven that hypoxia effects in the TME are mediated by exosomes, with the occasional formation of feedback loops. In this review, we equally focus on the biogenesis and heterogeneity of cancer-derived exosomes and their functions under hypoxia and describe the known and potential mechanism ascribed to exosomes and hypoxia. Notably, we call attention to the size change of hypoxic cancer cell-derived exosomes, a characteristic long neglected, and propose some possible effects of this size change. Finally, jointly considering recent developments in the understanding of exosomes and tumors, we describe noteworthy problems in this field that urgently need to be solved for better research and clinical application.
Display omitted
•Ferroptosis attract increasingly attention with a process involving many factors.•Negative regulator of ferroptosis such as GPX4, NRF2 can promote cancer resistance.•High metastasis ...and resistant cancer are vulnerable to ferroptosis inducer treatment.•Synthetic compounds and clinical drugs can used for resistant cancer by ferroptosis.•The combination of nanoparticle induced ferroptosis can be used for resistant cancer.
The development of chemotherapy drugs has promoted anticancer treatment, but the effect on tumours is not clear because of treatment resistance; thus, it is necessary to further understand the mechanism of cell death to explore new therapeutic targets. As a new type of programmed cell death, ferroptosis is increasingly being targeted in the treatment of many cancers with clinical drugs and experimental compounds. Ferroptosis is stimulated in tumours with inherently high levels of ferrous ions by a reaction with abundant polyunsaturated fatty acids and the inhibition of antioxidant enzymes, which can overcome treatment resistance in cancers mainly through GPX4. In this review, we focus on the intrinsic cellular regulators against ferroptosis in cancer resistance, such as GPX4, NRF2 and the thioredoxin system. We summarize the application of novel compounds and drugs to circumvent treatment resistance. We also introduce the application of nanoparticles for the treatment of resistant cancers. In conclusion, targeting ferroptosis represents a considerable strategy for resistant cancer treatment.
Sorafenib is a multi-kinase inhibitor that is used as a standard treatment for advanced hepatocellular carcinoma (HCC). However, the mechanism of sorafenib resistance in HCC is still unclear. It has ...been shown that CISD2 expression is related to the progression and poor prognosis of HCC. Here, we show a new role for CISD2 in sorafenib resistance in HCC.
Bioinformatic analysis was used to detect the expression of negative regulatory genes of ferroptosis in sorafenib-resistant samples. The concentration gradient method was used to establish sorafenib-resistant HCC cells. Western blot was used to detect the protein expression of CISD2, LC3, ERK, PI3K, AKT, mTOR, and Beclin1 in HCC samples. Quantitative real-time PCR (qPCR) was used to detect gene expression. CISD2 shRNA and Beclin1 shRNA were transfected to knock down the expression of the corresponding genes. Cell viability was detected by a CCK-8 assay. ROS were detected by DCFH-DA staining, and MDA and GSH were detected with a Lipid Peroxidation MDA Assay Kit and Micro Reduced Glutathione (GSH) Assay Kit, respectively. Flow cytometry was used to detect apoptosis and the levels of ROS and iron ions.
CISD2 was highly expressed in HCC cells compared with normal cells and was associated with poor prognosis in patients. Knockdown of CISD2 promoted a decrease in the viability of drug-resistant HCC cells. CISD2 knockdown promoted sorafenib-induced ferroptosis in resistant HCC cells. The levels of ROS, MDA, and iron ions increased, but the change in GSH was not obvious. Knockdown of CISD2 promoted uncontrolled autophagy in resistant HCC cells. Inhibition of autophagy attenuated CISD2 knockdown-induced ferroptosis. The autophagy promoted by CISD2 knockdown was related to Beclin1. When CISD2 and Beclin1 were inhibited, the effect on ferroptosis was correspondingly weakened.
Inhibition of CISD2 promoted sorafenib-induced ferroptosis in resistant cells, and this process promoted excessive iron ion accumulation through autophagy, leading to ferroptosis. The combination of CISD2 inhibition and sorafenib treatment is an effective therapeutic strategy for resistant HCC.
Background Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been ...confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear. Methods The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments. Results We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression. Conclusions Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression. Keywords: LncRNAs, Exosome, Multivesicular body, Invadopodia, Hepatocellular carcinoma
Tumor progression involves invasion, migration, metabolism, autophagy, exosome secretion, and drug resistance. Cargos transported by membrane vesicle trafficking underlie all of these processes. Rab ...GTPases, which, through coordinated and dynamic intracellular membrane trafficking alongside cytoskeletal pathways, determine the maintenance of homeostasis and a series of cellular functions. The mechanism of vesicle movement regulated by Rab GTPases plays essential roles in cancers. Therefore, targeting Rab GTPases to adjust membrane trafficking has the potential to become a novel way to adjust cancer treatment. In this review, we describe the characteristics of Rab GTPases; in particular, we discuss the role of their activation in the regulation of membrane transport and provide examples of Rab GTPases regulating membrane transport in tumor progression. Finally, we discuss the clinical implications and the potential as a cancer therapeutic target of Rab GTPases.
Dredged sediment poses significant challenges for transportation and subsequent treatment due to its high water content and large volume. Coagulation, a common method of dewatering, can significantly ...enhance the dewatering performance of dredged sediment. This study synthesized a cationic starch-based flocculant starch-3-chloro-2-hydroxypropyl trimethylammonium chloride (St-CTA) through etherification for the flocculation dewatering of dredged sediment. The effectiveness and mechanism of St-CTA as a dewatering flocculant for dredged sediment were investigated. The results demonstrated that when the dosage of St-CTA was 12 mg g
−1
TSS (total suspended solids), the dehydration property of dredged sediment substantially improved, with the specific resistance to filtration (SRF) decreasing by 93.3%, the capillary suction time (CST) by 93.5%, and the water content of the filter cake (WC) by 9.7%. The removal rate of turbidity of the supernatant from the conditioned dredged sediment reached 99.6%, accelerating the settling speed and effectively capturing and separating fine particles from the sediment. St-CTA significantly increased the median particle size (D50), altered the microstructure and extracellular polymeric substances (EPS) of the flocs, and increased the fractal dimension of the flocs, making them more compact and conducive to the formation of drainage channels. These findings confirm the feasibility of using potentially environmentally friendly St-CTA as a rapid dewatering conditioning agent for sediment.
Starch-based flocculants markedly improve the dewatering performance of dredged sediments, altering their rheology, and zeta potential among other relevant metrics.
The tumor microenvironment represents a dynamically composed matrix into which cancer cells and many other cell types are embedded to form organ-like structures. The tumor immune microenvironment ...(TIME), composed of immune cells, is an inseparable part of the tumor microenvironment. Extracellular vesicles (EVs) participate in the occurrence and development of tumors by delivering various biologically active molecules between cells; their role in cancer immune escape in particular has been widely proven. EVs can carry a wide array of cargo, such as non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, which are selectively loaded by EVs, secreted, and transported to participate in the proliferation of immune cells. Hence, strategies to specifically target EV-ncRNAs could be attractive therapeutic options. In this review, we summarize the current research on the role of EV-ncRNAs in cancer immune escape, and discuss the latest research on the function and regulation mechanism of EV-ncRNAs in cancer immune escape, highlighting and elucidating the potential clinical applications of EV-ncRNAs, including in diagnosis and immunotherapy.
•The biology of extracellular vesicles.•The biological function of EV-ncRNAs in cancer immune escape.•EV-ncRNAs serve as promising biomarkers.•The potential application of EV-ncRNAs in cancer immunotherapy.
Intracellular organelle cross-talk is a new and important research area. Under stress conditions, the coordinated action of the autophagy and endosomal systems in tumor cells is essential for ...maintaining cellular homeostasis and survival. The activation of the IκB kinase (IKK) complex is also involved in the regulation of stress and homeostasis in tumor cells. Here, we try to explore the effects of constitutively active IKKβ subunits (CA-IKKβ) on autophagy and endosomal system interactions. We confirm that CA-IKKβ induces accumulation of autophagosomes and their fusion with MVBs to form amphisomes in cancer cells, and also drives the release of EVs containing autophagy components through an amphisome-dependent mechanism. We further demonstrate that CA-IKKβ inhibits the expression of RAB7, thereby weakening the lysosomal-dependent degradation pathway. CA-IKKβ also induces phosphorylation of SNAP23 at Ser95 instead of Ser110, which further promotes amphisome-plasma membrane fusion and sEV secretion. These results indicate that CA-IKKβ drives the formation and transport of amphisomes, thereby regulating tumor cell homeostasis, which may illuminate a special survival mechanism in tumor cells under stress.
•IKKβ activation promotes extracellular vesicle secretion in tumor cells.•IKKβ activation induces amphisomes formation via fusion of autophagosomes with MVBs in tumor cells.•IKKβ controls autophagy-associated proteins secretion through an amphisome-dependent mechanism.•IKKβ regulates RAB7 mRNA levels and SNAP23 phosphorylation.
Phase change material (PCM) can be integrated into floor heating system to store excess heat, releasing it when needed, thus effectively reducing the mismatch between energy supply and demand. In ...this study, a double pipe PCM floor heating system with three independent heating modules was proposed for clean energy heating in rural China. A 26-day experimental study was conducted to study the operation effect of the system under four different strategies. Strategy 1: partial power operation strategy; Strategy 2: daytime energy storage strategy; Strategy 3: nocturnal energy storage strategy; and Strategy 4: phased energy storage strategy. In the early stage of heating, the average temperature of experiment room was 18.9 °C and the daily temperature fluctuation was controlled within 2.1 °C, which showed an effective guarantee of indoor comfort under Strategy 1. In the late stage of heating, the differences in indoor temperature fluctuations could be caused by changes in outdoor climate and operation strategies. And operating strategy had less impact on indoor temperature distribution. Moreover, the experiment results revealed that the system could provide a comfortable indoor thermal environment while adjusting operational strategies. And the 3 °C average daily temperature fluctuation confirmed the feasibility of creating a comfortable environment with gentle temperature fluctuations via the PCM floor intermittent heating.
•A double pipe PCM floor heating system with three independent modules was proposed.•Operation effects of the system under four different strategies were investigated.•Indoor temperature can be evenly distributed regardless of the adopted strategy.•The system can ensure indoor thermal comfort while adjusting operation strategies.•The average indoor daily temperature fluctuation was 1.8 °C; the minimum was 3.0 °C.
PDF
