The role of exosomes in the molecular mechanisms of metastasis: Focusing on EMT and cancer stem cells

Babaei, Ghader; Vostakolaei, Mehdi Asghari; Bazl, Masumeh Rajabi; Aziz, Shiva Gholizadeh‐Ghaleh; Gholipour, Elham; Nejati-Koshki, Kazem

doi:10.1016/j.lfs.2022.121103

Cited by 10 publications

(4 citation statements)

References 143 publications

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“…Further GSEA analysis showed that in high ZBTB9 expression samples, the G2M checkpoint, epithelial-mesenchymal transition, E2F targets, and KRAS-related signaling pathways were significantly activated, which has been reported to participate in tumor proliferation and progression [36,37]. In addition, the investigation of the correlation between ZBTB9 and KRAS signaling pathway demonstrated that ZBTB9 was evidently associated with MAPK1, NRAS, SHP2, SOS1, and KRAS2 (all play imperative roles in KRAS pathway [38][39][40]), suggesting that the malignant biological behaviors under ZBTB9 upregulation were probably mediating through this pathways.…”

Section: Discussionmentioning

confidence: 99%

Identification of ZBTB9 as a potential therapeutic target against dysregulation of tumor cells proliferation and a novel biomarker in Liver Hepatocellular Carcinoma

Zhang

et al. 2022

J Transl Med

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Background Zinc finger and bric-a-brac/tramtrack/broad (ZBTB) domain-containing proteins have been reported to be associated with many tumors’ development. However, in tumor initiation and progression, the role of ZBTB9, one of the protein family, and its prognostic value were yet to be elucidated in Liver Hepatocellular Carcinoma (LIHC). Methods We used R software and online bioinformatics analysis tools such as GEPIA2, cBioPortal, TIMER2, Metascape, UALCAN, STRING, TISIDB, and COSMIC to investigate ZBTB9’s characteristics and function in LIHC, including abnormal expression, carcinogenic role, related signaling pathways and prognostic value. Furthermore, cell experiments (such as formation, wound healing, and transwell assays) and analyses based on clinical samples (such as immunohistochemistry (IHC) and promoter methylation analysis) were conducted to verify pivotal conclusions. Results ZBTB9 was overexpressed in LIHC samples compared to adjacent normal tissues. Through the analysis of genomic alteration and promoter hypomethylation, the clinical value and etiology of abnormal expression of ZBTB9 were preliminarily exlpored. Subsequent evidence showed that it could result in tumor progression and poor prognosis via activating cell cycle, DNA repair, MYC, and KRAS-associated signaling pathways as well as rendering immune dysregulation. After the knockdown of ZBTB9, evidently inhibited capacities of tumor cells proliferation and migration were observed. These results together indicated that ZBTB9 could be a promising prognostic biomarker and had the potential value to offer novel therapeutic targets for LIHC treatment. Conclusions ZBTB9 was identified as a novel biomarker to predict the prognosis and tumor progression in LIHC, and a promising therapeutic target to invert tumor development.

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Section: Discussionmentioning

confidence: 99%

Identification of ZBTB9 as a potential therapeutic target against dysregulation of tumor cells proliferation and a novel biomarker in Liver Hepatocellular Carcinoma

Zhang

et al. 2022

J Transl Med

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“…Firstly, EVs can affect the cell interactions and signal transduction in TME by releasing bioactive molecules, thus regulating the process of GC metastasis (Zhang et al, 2021b;Li et al, 2023b). Secondly, the molecules released by EVs, such as Frontiers in Cell and Developmental Biology frontiersin.org metastasis-related proteins and non-coding RNAs, can regulate the EMT and MMT of GC cells, enhance the metastatic ability of GC (Deng et al, 2017;Babaei et al, 2022;Ang et al, 2023). In addition, immune regulatory molecules contained in EVs can regulate tumor immune escape and immune suppression, thus affecting the immune recognition and clearance of GC cells and affecting their metastasis (Kiya et al, 2023;Yi et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

The biological role of extracellular vesicles in gastric cancer metastasis

Lei,

Cai,

Zhang

et al. 2024

Front. Cell Dev. Biol.

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Gastric cancer (GC) is a tumor characterized by high incidence and mortality, with metastasis being the primary cause of poor prognosis. Extracellular vesicles (EVs) are an important intercellular communication medium. They contain bioactive substances such as proteins, nucleic acids, and lipids. EVs play a crucial biological role in the process of GC metastasis. Through mechanisms such as remodeling the tumor microenvironment (TME), immune suppression, promoting angiogenesis, and facilitating epithelial–mesenchymal transition (EMT) and mesothelial–mesenchymal transition (MMT), EVs promote invasion and metastasis in GC. Further exploration of the biological roles of EVs will contribute to our understanding of the mechanisms underlying GC metastasis and may provide novel targets and strategies for the diagnosis and treatment of GC. In this review, we summarize the mechanisms by which EVs influence GC metastasis from four aspects: remodeling the TME, modulating the immune system, influencing angiogenesis, and modulating the processes of EMT and MMT. Finally, we briefly summarized the organotropism of GC metastasis as well as the potential and limitations of EVs in GC.

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“…Studies have demonstrated that exosomes play a fundamental role in cells to communicate with neighboring or with distant cells [ 23 , 24 ]. Due to exosomes’ wide distribution in various human body fluids (blood, urine, saliva, cerebrospinal fluid, ascites, follicular fluid, and joint fluid), exosomes are regarded as ideal non-invasive biomarkers for early disease diagnosis [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Exosomal hsa-miR-151a-3p and hsa-miR-877-5p are potential novel biomarkers for predicting bone metastasis in lung cancer

Zhao,

Jia,

Wang

et al. 2023

Aging

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Exosomal miRNAs (exo-miRNAs) have arisen as novel diagnostic biomarkers for various cancers. However, few reports on exo-miRNAs related to bone metastasis (BM) in lung cancer exist. This study aims to screen out key exo-miRNAs and estimate their prognostic values for predicting BM in lung cancer. The differentially expressed exo-miRNAs between the highly-metastatic (95D) and lowly-metastatic (A549) human lung cancer cell lines were comprehensively analyzed using high-throughput sequencing followed by bioinformatic analyses. 29 candidate exo-miRNAs were identified, and 101 BM-related target genes were predicted. Enrichment analysis revealed that these target genes were mainly involved in regulating transcription and pathways in cancer. An exosomal miRNA-mRNA regulatory network consisting of 7 key miRNAs and 10 hub genes was constructed. Further function analysis indicated that these 10 hub genes were mainly enriched in regulating cancer’s apoptosis and central carbon metabolism. The survival analysis indicated that 7 of 10 hub genes were closely related to prognosis. Mutation analysis showed that lung cancer patients presented certain genetic alterations in the 7 real hub genes. GSEA for a single hub gene suggested that 6 of 7 real hub genes had close associations with lung cancer development. Finally, ROC analysis revealed that hsa-miR-151a-3p and hsa-miR-877-5p provided high diagnostic accuracy in discriminating patients with bone metastasis (BM+) from patients without bone metastasis (BM-). These findings provided a comprehensive analysis of exo-miRNAs and target genes in the regulatory network of BM in lung cancer. In particular, hsa-miR-151a-3p and hsa-miR-877-5p may be novel biomarkers for predicting BM in lung cancer.

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The role of exosomes in the molecular mechanisms of metastasis: Focusing on EMT and cancer stem cells

Cited by 10 publications

References 143 publications

Identification of ZBTB9 as a potential therapeutic target against dysregulation of tumor cells proliferation and a novel biomarker in Liver Hepatocellular Carcinoma

Identification of ZBTB9 as a potential therapeutic target against dysregulation of tumor cells proliferation and a novel biomarker in Liver Hepatocellular Carcinoma

The biological role of extracellular vesicles in gastric cancer metastasis

Exosomal hsa-miR-151a-3p and hsa-miR-877-5p are potential novel biomarkers for predicting bone metastasis in lung cancer

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