Role of Herbal Medicine/Phyto-Therapy in Cancer Prevention by Inhibiting Epithelial-Mesenchymal Transition (EMT) Pathways

2021 ◽  
pp. 215-234
Author(s):  
Rekha Gahtori ◽  
Ashutosh Paliwal
Keyword(s):  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Raw Materials ◽  
Human Life ◽  
Developed Countries ◽  
Mesenchymal Transition ◽  
Synthetic Drugs ◽  
Extracellular Signals ◽  
Different Levels

Human life is surrounded and dependent on its environment. Human civilization is nurtured by nature as it provides raw materials that are used in the manufacturing of various essential products like medicine, food items, etc. Not only developing countries but developed countries also depend on herbal-based medications. Cancer is a global health burden. Epithelial-mesenchymal-transition (EMT) plays a key role in cancer progression and is also stimulated by different extracellular signals and could be regulated at different levels. Conventional therapies exhibit a cytotoxic effect, which encourages the development of a new approach that could be used with synthetic drugs. Phytotherapy emerged as an effective weapon against cancer. Herbal drugs directly target different signaling pathways that promote EMT and eventually lead to cancer.

scholarly journals The Epithelial–Mesenchymal Transition at the Crossroads between Metabolism and Tumor Progression

2022 ◽  
Vol 23 (2) ◽  
pp. 800
Author(s):  
Monica Fedele ◽  
Riccardo Sgarra ◽  
Sabrina Battista ◽  
Laura Cerchia ◽  
Guidalberto Manfioletti
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Energy Demand ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Epithelial Phenotype ◽  
Plastic Process ◽  
Mesenchymal Epithelial Transition

The transition between epithelial and mesenchymal phenotype is emerging as a key determinant of tumor cell invasion and metastasis. It is a plastic process in which epithelial cells first acquire the ability to invade the extracellular matrix and migrate into the bloodstream via transdifferentiation into mesenchymal cells, a phenomenon known as epithelial–mesenchymal transition (EMT), and then reacquire the epithelial phenotype, the reverse process called mesenchymal–epithelial transition (MET), to colonize a new organ. During all metastatic stages, metabolic changes, which give cancer cells the ability to adapt to increased energy demand and to withstand a hostile new environment, are also important determinants of successful cancer progression. In this review, we describe the complex interaction between EMT and metabolism during tumor progression. First, we outline the main connections between the two processes, with particular emphasis on the role of cancer stem cells and LncRNAs. Then, we focus on some specific cancers, such as breast, lung, and thyroid cancer.

scholarly journals Transcription Factors in Cancer Development and Therapy

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2296 ◽  
Author(s):  
Kanchan Vishnoi ◽  
Navin Viswakarma ◽  
Ajay Rana ◽  
Basabi Rana
Keyword(s):  
Transcription Factors ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Constitutive Expression ◽  
Comprehensive Overview ◽  
Growth And Survival ◽  
Mesenchymal Transition ◽  
Activation Of Transcription ◽  
Target Cancer

Cancer is a multi-step process and requires constitutive expression/activation of transcription factors (TFs) for growth and survival. Many of the TFs reported so far are critical for carcinogenesis. These include pro-inflammatory TFs, hypoxia-inducible factors (HIFs), cell proliferation and epithelial–mesenchymal transition (EMT)-controlling TFs, pluripotency TFs upregulated in cancer stem-like cells, and the nuclear receptors (NRs). Some of those, including HIFs, Myc, ETS-1, and β-catenin, are multifunctional and may regulate multiple other TFs involved in various pro-oncogenic events, including proliferation, survival, metabolism, invasion, and metastasis. High expression of some TFs is also correlated with poor prognosis and chemoresistance, constituting a significant challenge in cancer treatment. Considering the pivotal role of TFs in cancer, there is an urgent need to develop strategies targeting them. Targeting TFs, in combination with other chemotherapeutics, could emerge as a better strategy to target cancer. So far, targeting NRs have shown promising results in improving survival. In this review, we provide a comprehensive overview of the TFs that play a central role in cancer progression, which could be potential therapeutic candidates for developing specific inhibitors. Here, we also discuss the efforts made to target some of those TFs, including NRs.

scholarly journals Role of cellular cytoskeleton in epithelial-mesenchymal transition process during cancer progression

2015 ◽  
Vol 3 (5) ◽  
pp. 603-610 ◽  
Author(s):  
BO SUN ◽  
YANTIAN FANG ◽  
ZHENYANG LI ◽  
ZONGYOU CHEN ◽  
JIANBIN XIANG
Keyword(s):  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Transition Process ◽  
Mesenchymal Transition ◽  
Cellular Cytoskeleton

scholarly journals Possible Role of Sonic Hedgehog and Epithelial-Mesenchymal Transition in Renal Cell Cancer Progression

2013 ◽  
Vol 54 (8) ◽  
pp. 547 ◽  
Author(s):  
Hosny M. Behnsawy ◽  
Katsumi Shigemura ◽  
Fatma Y. Meligy ◽  
Fukashi Yamamichi ◽  
Masuo Yamashita ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Cancer Progression ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cell Cancer ◽  
Mesenchymal Transition

scholarly journals Mechanistic Insights Delineating the Role of Cholesterol in Epithelial Mesenchymal Transition and Drug Resistance in Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Naaziyah Abdulla ◽  
C. Theresa Vincent ◽  
Mandeep Kaur
Keyword(s):  
Drug Resistance ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Cholesterol Metabolism ◽  
Cholesterol Content ◽  
Multi Drug Resistance ◽  
Mesenchymal Transition ◽  
Proposed Model

Despite the significant advancements made in targeted anti-cancer therapy, drug resistance constitutes a multifaceted phenomenon leading to therapy failure and ultimately mortality. Emerging experimental evidence highlight a role of cholesterol metabolism in facilitating drug resistance in cancer. This review aims to describe the role of cholesterol in facilitating multi-drug resistance in cancer. We focus on specific signaling pathways that contribute to drug resistance and the link between these pathways and cholesterol. Additionally, we briefly discuss the molecular mechanisms related to the epithelial-mesenchymal transition (EMT), and the documented link between EMT, metastasis and drug resistance. We illustrate this by specifically focusing on hypoxia and the role it plays in influencing cellular cholesterol content following EMT induction. Finally, we provide a proposed model delineating the crucial role of cholesterol in EMT and discuss whether targeting cholesterol could serve as a novel means of combatting drug resistance in cancer progression and metastasis.

scholarly journals Communication Between Epithelial–Mesenchymal Plasticity and Cancer Stem Cells: New Insights Into Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaobo Zheng ◽  
Fuzhen Dai ◽  
Lei Feng ◽  
Hong Zou ◽  
Li Feng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Epithelial Mesenchymal Transition ◽  
Current Knowledge ◽  
Mesenchymal Transition ◽  
Binary Model ◽  
Epithelial Phenotype

The epithelial–mesenchymal transition (EMT) is closely associated with the acquisition of aggressive traits by carcinoma cells and is considered responsible for metastasis, relapse, and chemoresistance. Molecular links between the EMT and cancer stem cells (CSCs) have indicated that EMT processes play important roles in the expression of CSC-like properties. It is generally thought that EMT-related transcription factors (EMT-TFs) need to be downregulated to confer an epithelial phenotype to mesenchymal cells and increase cell proliferation, thereby promoting metastasis formation. However, the genetic and epigenetic mechanisms that regulate EMT and CSC activation are contradictory. Emerging evidence suggests that EMT need not be a binary model and instead a hybrid epithelial/mesenchymal state. This dynamic process correlates with epithelial–mesenchymal plasticity, which indicates a contradictory role of EMT during cancer progression. Recent studies have linked the epithelial–mesenchymal plasticity and stem cell-like traits, providing new insights into the conflicting relationship between EMT and CSCs. In this review, we examine the current knowledge about the interplay between epithelial–mesenchymal plasticity and CSCs in cancer biology and evaluate the controversies and future perspectives. Understanding the biology of epithelial–mesenchymal plasticity and CSCs and their implications in therapeutic treatment may provide new opportunities for targeted intervention.

scholarly journals Progression of prostate carcinoma is promoted by adipose stromal cell-secreted CXCL12 signaling in prostate epithelium

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Fei Su ◽  
Alexes C. Daquinag ◽  
Songyeon Ahn ◽  
Achinto Saha ◽  
Yulin Dai ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Prostate Carcinoma ◽  
Stromal Cells ◽  
Epithelial Mesenchymal Transition ◽  
Genetic Model ◽  
Clinical Sample ◽  
Cxcl12 Expression ◽  
Mesenchymal Transition ◽  
Prostate Epithelium

AbstractAggressiveness of carcinomas is linked with tumor recruitment of adipose stromal cells (ASC), which is increased in obesity. ASC promote cancer through molecular pathways not fully understood. Here, we demonstrate that epithelial–mesenchymal transition (EMT) in prostate tumors is promoted by obesity and suppressed upon pharmacological ASC depletion in HiMyc mice, a spontaneous genetic model of prostate cancer. CXCL12 expression in tumors was associated with ASC recruitment and localized to stromal cells expressing platelet-derived growth factor receptors Pdgfra and Pdgfrb. The role of this chemokine secreted by stromal cells in cancer progression was further investigated by using tissue-specific knockout models. ASC deletion of CXCL12 gene in the Pdgfr + lineages suppressed tumor growth and EMT, indicating stroma as the key source of CXCL12. Clinical sample analysis revealed that CXCL12 expression by peritumoral adipose stroma is increased in obesity, and that the correlating increase in Pdgfr/CXCL12 expression in the tumor is linked with decreased survival of patients with prostate carcinoma. Our study establishes ASC as the source of CXCL12 driving tumor aggressiveness and outlines an approach to treatment of carcinoma progression.

scholarly journals The Cancer Microbiota: EMT and Inflammation as Shared Molecular Mechanisms Associated with Plasticity and Progression

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Daniele Vergara ◽  
Pasquale Simeone ◽  
Marina Damato ◽  
Michele Maffia ◽  
Paola Lanuti ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Common Ground ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Malignant Progression ◽  
Pathogenic Microorganisms ◽  
Mesenchymal Transition ◽  
Host Interactions

With the advent of novel molecular platforms for high-throughput/next-generation sequencing, the communities of commensal and pathogenic microorganisms that inhabit the human body have been defined in depth. In the last decade, the role of microbiota-host interactions in driving human cancer plasticity and malignant progression has been well documented. Germ-free preclinical models provided an invaluable tool to demonstrate that the human microbiota can confer susceptibility to various types of cancer and can also modulate the host response to therapeutic treatments. Of interest, besides the detrimental effects of dysbiosis on cancer etiopathogenesis, specific microorganisms have been shown to exert protective activities against cancer growth. This has strong clinical implications, as restoration of the physiologic microbiota is being rapidly implemented as a novel anticancer therapeutic strategy. Here, we reviewed past and recent literature depicting the role of microbiota-host interactions in modulating key molecular mechanisms that drive human cancer plasticity and lead to malignant progression. We analyzed microbiota-host interactions occurring in the gut as well as in other anatomic sites, such as oral and nasal cavities, lungs, breast, esophagus, stomach, reproductive tract, and skin. We revealed a common ground of biological alterations and pathways modulated by a dysbiotic microbiota and potentially involved in the control of cancer progression. The molecular mechanisms most frequently affected by the pathogenic microorganisms to induce malignant progression involve epithelial-mesenchymal transition- (EMT-) dependent barrier alterations and tumor-promoting inflammation. This evidence may pave the way to better stratify high-risk cancer patients based on unique microenvironmental/microbial signatures and to develop novel, personalized, biological therapies.

scholarly journals Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2300
Author(s):  
Rofaida Gaballa ◽  
Hamdy E. A. Ali ◽  
Mohamed O. Mahmoud ◽  
Johng S. Rhim ◽  
Hamed I. Ali ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Normal Subjects ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Aggressive Phenotype ◽  
Endogenous Expression

Although integrin alpha 2 subunit (ITGA2) mediates cancer progression and metastasis, its transfer by exosomes has not been investigated in prostate cancer (PCa). We aimed to determine the role of exosomal ITGA2 derived from castration-resistant PCa (CRPC) cells in promoting aggressive phenotypes in androgen receptor (AR)-positive cells. Exosomes were co-incubated with recipient cells and tested for different cellular assays. ITGA2 was enriched in exosomes derived from CRPC cells. Co-culture of AR-positive cells with CRPC-derived exosomes increased their proliferation, migration, and invasion by promoting epithelial-mesenchymal transition, which was reversed via ITGA2 knockdown or inhibition of exosomal uptake by methyl-β-cyclodextrin (MβCD). Ectopic expression of ITGA2 reproduced the effect of exosomal ITGA2 in PCa cells. ITGA2 transferred by exosomes exerted its effect within a shorter time compared to that triggered by its endogenous expression. The difference of ITGA2 protein expression in localized tumors and those with lymph node metastatic tissues was indistinguishable. Nevertheless, its abundance was higher in circulating exosomes collected from PCa patients when compared with normal subjects. Our findings indicate the possible role of the exosomal-ITGA2 transfer in altering the phenotype of AR-positive cells towards more aggressive phenotype. Thus, interfering with exosomal cargo transfer may inhibit the development of aggressive phenotype in PCa cells.

scholarly journals EMT-induced cell mechanical changes enhance mitotic rounding strength

2019 ◽  
Author(s):  
Kamran Hosseini ◽  
Anna Taubenberger ◽  
Carsten Werner ◽  
Elisabeth Fischer-Friedrich
Keyword(s):  
Cancer Progression ◽  
Mitotic Spindle ◽  
Rho Gtpases ◽  
Epithelial Mesenchymal Transition ◽  
Surrounding Tissue ◽  
Animal Cells ◽  
Mesenchymal Transition ◽  
Round Shape ◽  
Actomyosin Contractility

AbstractTo undergo mitosis successfully, most animal cells need to acquire a round shape to provide space for the mitotic spindle. This mitotic rounding relies on mechanical deformation of surrounding tissue and is driven by forces emanating from actomyosin contractility. Cancer cells are able to maintain successful mitosis in mechanically challenging environments such as the increasingly crowded environment of a growing tumor, thus, suggesting an enhanced ability of mitotic rounding in cancer. Here, we show that epithelial mesenchymal transition (EMT), a hallmark of cancer progression and metastasis, gives rise to cell-mechanical changes in breast epithelial cells. These changes are opposite in interphase and mitosis and correspond to an enhanced mitotic rounding strength. Furthermore, we show that cell-mechanical changes correlate with a strong EMT-induced change in the activity of Rho GTPases RhoA and Rac1. Accordingly, we find that Rac1 inhibition rescues the EMT-induced cortex-mechanical phenotype. Our findings hint at a new role of EMT in successful mitotic rounding and division in mechanically confined environments such as a growing tumor.

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