scholarly journals Interplay among SNAIL Transcription Factor, MicroRNAs, Long Non-Coding RNAs, and Circular RNAs in the Regulation of Tumor Growth and Metastasis

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 209 ◽  
Author(s):  
Klaudia Skrzypek ◽  
Marcin Majka
Keyword(s):  
Transcription Factor ◽  
Tumor Growth ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Metabolism ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Non Coding Rnas ◽  
Tumor Growth And Metastasis ◽  
Novel Therapeutic Strategies

SNAIL (SNAI1) is a zinc finger transcription factor that binds to E-box sequences and regulates the expression of genes. It usually acts as a gene repressor, but it may also activate the expression of genes. SNAIL plays a key role in the regulation of epithelial to mesenchymal transition, which is the main mechanism responsible for the progression and metastasis of epithelial tumors. Nevertheless, it also regulates different processes that are responsible for tumor growth, such as the activity of cancer stem cells, the control of cell metabolism, and the regulation of differentiation. Different proteins and microRNAs may regulate the SNAIL level, and SNAIL may be an important regulator of microRNA expression as well. The interplay among SNAIL, microRNAs, long non-coding RNAs, and circular RNAs is a key event in the regulation of tumor growth and metastasis. This review for the first time discusses different types of regulation between SNAIL and non-coding RNAs with a focus on feedback loops and the role of competitive RNA. Understanding these mechanisms may help develop novel therapeutic strategies against cancer based on microRNAs.

scholarly journals Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers

2022 ◽  
Vol 23 (2) ◽  
pp. 930
Author(s):  
Ba Da Yun ◽  
Ye Ji Choi ◽  
Seung Wan Son ◽  
Gabriel Adelman Cipolla ◽  
Fernanda Costa Brandão Berti ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Cell Communication ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Circular Rnas ◽  
Gastrointestinal Cancers ◽  
Gastrointestinal Malignancies ◽  
Mesenchymal Transition ◽  
Novel Therapeutic Strategies

Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) are differentially expressed in gastrointestinal cancers. These noncoding RNAs (ncRNAs) regulate a variety of cellular activities by physically interacting with microRNAs and proteins and altering their activity. It has also been suggested that exosomes encapsulate circRNAs and lncRNAs in cancer cells. Exosomes are then discharged into the extracellular environment, where they are taken up by other cells. As a result, exosomal ncRNA cargo is critical for cell–cell communication within the cancer microenvironment. Exosomal ncRNAs can regulate a range of events, such as angiogenesis, metastasis, immune evasion, drug resistance, and epithelial-to-mesenchymal transition. To set the groundwork for developing novel therapeutic strategies against gastrointestinal malignancies, a thorough understanding of circRNAs and lncRNAs is required. In this review, we discuss the function and intrinsic features of oncogenic circRNAs and lncRNAs that are enriched within exosomes.

scholarly journals Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin

2007 ◽  
Vol 204 (12) ◽  
pp. 2935-2948 ◽  
Author(s):  
Kevin G. Leong ◽  
Kyle Niessen ◽  
Iva Kulic ◽  
Afshin Raouf ◽  
Connie Eaves ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Poor Prognosis ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Tumors ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Slug Expression ◽  
Tumor Growth And Metastasis ◽  
Notch Activation ◽  
E Cadherin

Aberrant expression of Jagged1 and Notch1 are associated with poor outcome in breast cancer. However, the reason that Jagged1 and/or Notch overexpression portends a poor prognosis is unknown. We identify Slug, a transcriptional repressor, as a novel Notch target and show that elevated levels of Slug correlate with increased expression of Jagged1 in various human cancers. Slug was essential for Notch-mediated repression of E-cadherin, which resulted in β-catenin activation and resistance to anoikis. Inhibition of ligand-induced Notch signaling in xenografted Slug-positive/E-cadherin–negative breast tumors promoted apoptosis and inhibited tumor growth and metastasis. This response was associated with down-regulated Slug expression, reexpression of E-cadherin, and suppression of active β-catenin. Our findings suggest that ligand-induced Notch activation, through the induction of Slug, promotes tumor growth and metastasis characterized by epithelial-to-mesenchymal transition and inhibition of anoikis.

scholarly journals TIMP-2 suppresses tumor growth and metastasis in murine model of triple-negative breast cancer

2019 ◽  
Vol 41 (3) ◽  
pp. 313-325 ◽  
Author(s):  
David Peeney ◽  
Sandra M Jensen ◽  
Nadia P Castro ◽  
Sarvesh Kumar ◽  
Silvia Noonan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Signaling Pathways ◽  
Triple Negative Breast Cancer ◽  
Primary Tumor ◽  
Epithelial To Mesenchymal Transition ◽  
Triple Negative ◽  
Metastasis Suppressor ◽  
Mesenchymal Transition ◽  
Tumor Growth And Metastasis

Abstract Metastasis is the primary cause of treatment failures and mortality in most cancers. Triple-negative breast cancer (TNBC) is refractory to treatment and rapidly progresses to disseminated disease. We utilized an orthotopic mouse model that molecularly and phenotypically resembles human TNBC to study the effects of exogenous, daily tissue inhibitor of metalloproteinase-2 (TIMP-2) treatment on tumor growth and metastasis. Our results demonstrated that TIMP-2 treatment maximally suppressed primary tumor growth by ~36–50% and pulmonary metastasis by >92%. Immunostaining assays confirmed disruption of the epithelial to mesenchymal transition (EMT) and promotion of vascular integrity in primary tumor tissues. Immunostaining and RNA sequencing analysis of lung tissue lysates from tumor-bearing mice identified significant changes associated with metastatic colony formation. Specifically, TIMP-2 treatment disrupts periostin localization and critical cell-signaling pathways, including canonical Wnt signaling involved in EMT, as well as PI3K signaling, which modulates proliferative and metastatic behavior through p27 phosphorylation/localization. In conclusion, our study provides evidence in support of a role for TIMP-2 in suppression of triple-negative breast cancer growth and metastasis through modulation of the epithelial to mesenchymal transition, vascular normalization, and signaling pathways associated with metastatic outgrowth. Our findings suggest that TIMP-2, a constituent of the extracellular matrix in normal tissues, may have both direct and systemic antitumor and metastasis suppressor effects, suggesting potential utility in the clinical management of breast cancer progression.

scholarly journals Epigenetic Associations between lncRNA/circRNA and miRNA in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2622 ◽  
Author(s):  
Tae-Su Han ◽  
Keun Hur ◽  
Hyun-Soo Cho ◽  
Hyun Seung Ban
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Target Genes ◽  
Circular Rnas ◽  
Cancer Cell Growth ◽  
Mesenchymal Transition ◽  
Downstream Target ◽  
Non Coding Rnas ◽  
Regulation Model

The three major members of non-coding RNAs (ncRNAs), named microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play an important role in hepatocellular carcinoma (HCC) development. Recently, the competing endogenous RNA (ceRNA) regulation model described lncRNA/circRNA as a sponge for miRNAs to indirectly regulate miRNA downstream target genes. Accumulating evidence has indicated that ceRNA regulatory networks are associated with biological processes in HCC, including cancer cell growth, epithelial to mesenchymal transition (EMT), metastasis, and chemoresistance. In this review, we summarize recent discoveries, which are specific ceRNA regulatory networks (lncRNA/circRNA-miRNA-mRNA) in HCC and discuss their clinical significance.

scholarly journals Zinc Finger Transcription Factor MZF1—A Specific Regulator of Cancer Invasion

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 223 ◽  
Author(s):  
Ditte Marie Brix ◽  
Knut Kristoffer Bundgaard Clemmensen ◽  
Tuula Kallunki
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Drug Targets ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Aberrant Gene Expression ◽  
Myeloid Zinc Finger ◽  
Aberrant Gene

Over 90% of cancer deaths are due to cancer cells metastasizing into other organs. Invasion is a prerequisite for metastasis formation. Thus, inhibition of invasion can be an efficient way to prevent disease progression in these patients. This could be achieved by targeting the molecules regulating invasion. One of these is an oncogenic transcription factor, Myeloid Zinc Finger 1 (MZF1). Dysregulated transcription factors represent a unique, increasing group of drug targets that are responsible for aberrant gene expression in cancer and are important nodes driving cancer malignancy. Recent studies report of a central involvement of MZF1 in the invasion and metastasis of various solid cancers. In this review, we summarize the research on MZF1 in cancer including its function and role in lysosome-mediated invasion and in the expression of genes involved in epithelial to mesenchymal transition. We also discuss possible means to target it on the basis of the current knowledge of its function in cancer.

scholarly journals Adipose-Derived Stem Cells Facilitate Ovarian Tumor Growth and Metastasis by Promoting Epithelial to Mesenchymal Transition Through Activating the TGF-β Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaowu Liu ◽  
Guannan Zhao ◽  
Xueyun Huo ◽  
Yaohong Wang ◽  
Gabor Tigyi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Growth ◽  
Ovarian Tumor ◽  
Epithelial To Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Migration And Invasion ◽  
Adipose Derived Stem Cells ◽  
Mesenchymal Transition ◽  
Tumor Growth And Metastasis

Adipose-derived stem cells (ADSC) are multipotent mesenchymal stem cells derived from adipose tissues and are capable of differentiating into multiple cell types in the tumor microenvironment (TME). The roles of ADSC in ovarian cancer (OC) metastasis are still not well defined. To understand whether ADSC contributes to ovarian tumor metastasis, we examined epithelial to mesenchymal transition (EMT) markers in OC cells following the treatment of the ADSC-conditioned medium (ADSC-CM). ADSC-CM promotes EMT in OC cells. Functionally, ADSC-CM promotes OC cell proliferation, survival, migration, and invasion. We further demonstrated that ADSC-CM induced EMT via TGF-β growth factor secretion from ADSC and the ensuing activation of the TGF-β pathway. ADSC-CM-induced EMT in OC cells was reversible by the TGF-β inhibitor SB431542 treatment. Using an orthotopic OC mouse model, we also provide the experimental evidence that ADSC contributes to ovarian tumor growth and metastasis by promoting EMT through activating the TGF-β pathway. Taken together, our data indicate that targeting ADSC using the TGF-β inhibitor has the therapeutic potential in blocking the EMT and OC metastasis.

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