Steps in metastasis: an updated review

Majidpoor, Jamal; Mortezaee, Keywan

doi:10.1007/s12032-020-01447-w

Cited by 189 publications

(144 citation statements)

References 158 publications

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“…The epithelial-mesenchymal transition (EMT) plays a key role in metastasis [ 120 ]. This mechanism is discussed in detail in many review articles [ 120 , 121 , 122 , 123 , 124 ]. Cell motility, migration, and invasion are also regulated by Notch, Wnt, and Hedgehog signaling pathways [ 125 ].…”

Section: Mechanisms Of Anticancer Activity Of Propolis and Its Compoundsmentioning

confidence: 99%

Anticancer Activity of Propolis and Its Compounds

2021

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Propolis is a natural material that honey bees (Apis mellifera) produce from various botanical sources. The therapeutic activity of propolis, including antibacterial, antifungal, and anti-inflammatory effects, have been known since antiquity. Cancer is one of the major burdens of disease worldwide, therefore, numerous studies are being conducted to develop new chemotherapeutic agents and treatments for cancer. Propolis is a rich source of biologically active compounds, which affect numerous signaling pathways regulating crucial cellular processes. The results of the latest research show that propolis can inhibit proliferation, angiogenesis, and metastasis of cancer cells and stimulate apoptosis. Moreover, it may influence the tumor microenvironment and multidrug resistance of cancers. This review briefly summarizes the molecular mechanisms of anticancer activity of propolis and its compounds and highlights the potential benefits of propolis to reduce the side effects of chemotherapy and radiotherapy.

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Section: Mechanisms Of Anticancer Activity Of Propolis and Its Compoundsmentioning

confidence: 99%

Anticancer Activity of Propolis and Its Compounds

2021

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“…The initiation of tumor metastasis depends on the interaction between tumor cells and stromal cells, and EMT occurs in single cells. Hybrid EMT occurs in collectively migrating cells [29]. These ndings suggest that EMT is closely related to tumor metastasis and recurrence.…”

Section: Discussionmentioning

confidence: 85%

Wnt Pathway-Related Three-mRNA Clinical Outcome Signature In Bladder Urothelial Carcinoma: Computational Biology And Experimental Analyses

Sun

Wang

et al. 2021

Preprint

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BackgroundThe Wnt signaling pathway is core to the growth of bladder tumors. Epithelial-to-mesenchymal transition (EMT) is significant for bladder tumor metastasis. Nevertheless, the relationship between the Wnt signaling pathway, outcomes of bladder cancer (BLCA), and the specific mechanisms driving immune infiltration have not been studied.MethodsWe obtained Wnt pathway-related gene mRNA and clinicopathological data from the Cancer Genome Atlas (TCGA). We obtained 34 genes that were greatly correlated with outcome using univariate Cox regression analysis and conducted a completely randomized data t-test to perform clinical staging. According to the single-sample gene set enrichment analysis (ssGSEA), the weighted correlation network analysis (WGCNA) was applied to identify relevant biological functions. Various subtypes were identified using consensus cluster analysis. Univariate Cox regression and least absolute shrinkage sum selection operator–Cox regression algorithm analysis were conducted on TCGA and Gene Expression Omnibus data to identify risk characteristics. The Kaplan–Meier method and receiver running feature curves were adopted to calculate overall survival. Single-sample gene set enrichment analysis (ssGSEA) was adopted for the assessment of the degree of immune infiltration. Then, we demonstrated the relationship between PPP2CB and EMT function in two cell lines. ResultsThirty-four Wnt signaling pathway-related genes were risk factors for BLCA outcome, and their expression levels differed by clinical stage. The co-expression of WGCNA showed the relationship between the Wnt signaling pathway and biological functions and was closely associated with EMT. We divided BLCA patients into two subtypes using consensus clustering. Survival curves and clinical analysis showed that the Wnt pathway enriched group had worse outcomes. The Wnt signature showed the significance of the outcome for MAPK10, PPP2CB, and RAC3. Based on these genes, the degree of immune infiltration was evaluated. Cell function experiments suggested that PPP2CB drives the proliferation and migration of BLCA cells.ConclusionWe found that Wnt signaling pathway-related genes can be used as prognostic risk factors for BLCA, and the Wnt signaling pathway is a cancer-promoting signaling pathway associated with EMT. We identified three critical genes: MAPK10, RAC3, and PPP2CB. The genes in these three Wnt signaling pathways are associated with tumor cell EMT and immune cell infiltration. The most important finding was that these three genes were independent prognostic factors for BLCA.

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“…CAF, cancer-associated fibroblast; CSC, cancer stem cell; M2, macrophage type 2; MDSC, myeloid-derived suppressor cell; TGF-β, transforming growth factorβ; Treg, regulatory T process beginning with the escape (invasion) of tumor cells and terminated by colonization within secondary sites. [45] CAFs are known as the guardian of tumor metastasis, and CSCs represent metastatic potency, both of which contribute to the formation of premetastatic niches (PMNs), [14] indicating cell-to-cell cross-talk between CAFs and tumor cells for promoting tumor metastasis. Immunosuppression is one of the key characteristics of PMNs, [46] which implies a greater tendency among cold tumors like the pancreas to pursue metastasis.…”

Section: Tme Hypoxia and Inflammation In Tumor Desmoplasia And Coldmentioning

confidence: 99%

Enriched cancer stem cells, dense stroma, and cold immunity: Interrelated events in pancreatic cancer

Mortezaee

2021

J Biochem & Molecular Tox

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Cold tumors generally show low mutational burden and low infiltration of effector T cells. The pancreas, prostate, ovary, breast, and colon are placed into the category of cold tumors. In such tumors, effector T cells are either excluded from the tumor area or taken away from being in contact with tumor cells. The stromal reaction in the form of desmoplasia is important for the pathogenesis of tumors like the pancreas. Besides acting as a barrier for the penetration of drugs into the tumor area, the dense stroma presumably creates an immunosuppressive tumor microenvironment (TME), which accounts for low responses from tumor to immunotherapy. Cancer stem cells (CSCs) are an important part of the immunosuppressive complex within the TME. The presence of CSCs within the TME is related negatively to the activity of the antitumor immune system. Here, the question is how desmoplastic aggregates can influence the functionality of CSCs for promoting a cold pancreatic tumor immunity? This review is aimed at responding to this question, the disruption of which can be an effective strategy for improving responses from cold tumors to immunotherapy.

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Steps in metastasis: an updated review

Cited by 189 publications

References 158 publications

Anticancer Activity of Propolis and Its Compounds

Anticancer Activity of Propolis and Its Compounds

Wnt Pathway-Related Three-mRNA Clinical Outcome Signature In Bladder Urothelial Carcinoma: Computational Biology And Experimental Analyses

Enriched cancer stem cells, dense stroma, and cold immunity: Interrelated events in pancreatic cancer

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