scholarly journals Missing Links in Epithelial-Mesenchymal Transition: Long Non-Coding RNAs Enter the Arena

2017 ◽  
Vol 44 (4) ◽  
pp. 1665-1680 ◽  
Author(s):  
Lei Wang ◽  
Fan Yang ◽  
Lin-Tao Jia ◽  
An-Gang Yang
Keyword(s):  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Biological Activities ◽  
Carcinoma Cells ◽  
Mesenchymal Transition ◽  
Master Regulators ◽  
A Cell ◽  
Non Coding Rnas ◽  
Biological Program

Cancer metastasis occurs through a series of sequential steps, which involves dissemination of tumor cells from a primary site and colonization in distant tissues. To promote the invasion-metastasis cascade, carcinoma cells usually initiate a cell-biological program called epithelial-mesenchymal transition (EMT), which is orchestrated by a set of master regulators, including TGF-β, Snail, ZEB and Twist families. The biological activities of these molecules are tightly regulated by a variety of cell-intrinsic pathways as well as extracellular cues. Recently, accumulating evidence indicates that long non-coding RNAs (lncRNAs) represent some of the most differentially expressed transcripts between primary and metastatic cancers. LncRNAs including MALAT1, HOTAIR, H19, LncRNA-ATB, and LincRNA-ROR have been reported to be involved in the process of EMT, mainly through cross-talking with master regulators of EMT. Thus, understanding the different and precise molecular mechanisms by which functional lncRNAs switch EMT on and off is important for opening up new avenues in lncRNA-directed diagnosis, prognosis, and therapeutic intervention against cancer.

Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 77-96
Author(s):  
T. Jeethy Ram ◽  
Asha Lekshmi ◽  
Thara Somanathan ◽  
K. Sujathan
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cellular Level ◽  
Clinical Samples ◽  
Innovative Strategy ◽  
Mesenchymal Transition ◽  
Galectin 3

Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.

scholarly journals SPNS2 Downregulation Induces EMT and Promotes Colorectal Cancer Metastasis via Activating AKT Signaling Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Lei Lv ◽  
Qiyi Yi ◽  
Ying Yan ◽  
Fengmei Chao ◽  
Ming Li
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Akt Inhibitor ◽  
Colon Adenoma ◽  
Mesenchymal Transition

Spinster homologue 2 (SPNS2), a transporter of S1P (sphingosine-1-phosphate), has been reported to mediate immune response, vascular development, and pathologic processes of diseases such as cancer via S1P signaling pathways. However, its biological functions and expression profile in colorectal cancer (CRC) is elusive. In this study, we disclosed that SPNS2 expression, which was regulated by copy number variation and DNA methylation of its promoter, was dramatically upregulated in colon adenoma and CRC compared to normal tissues. However, its expression was lower in CRC than in colon adenoma, and low expression of SPN2 correlated with advanced T/M/N stage and poor prognosis in CRC. Ectopic expression of SPNS2 inhibited cell proliferation, migration, epithelial–mesenchymal transition (EMT), invasion, and metastasis in CRC cell lines, while silencing SPNS2 had the opposite effects. Meanwhile, measuring the intracellular and extracellular level of S1P after overexpression of SPNS2 pinpointed a S1P-independent model of SPNS2. Mechanically, SPNS2 led to PTEN upregulation and inactivation of Akt. Moreover, AKT inhibitor (MK2206) abrogated SPNS2 knockdown-induced promoting effects on the migration and invasion, while AKT activator (SC79) reversed the repression of migration and invasion by SPNS2 overexpression in CRC cells, confirming the pivotal role of AKT for SPNS2’s function. Collectively, our study demonstrated the suppressor role of SPNS2 during CRC metastasis, providing new insights into the pathology and molecular mechanisms of CRC progression.

scholarly journals HNF1A recruits UTX to activate a differentiation program that suppresses pancreatic cancer

2019 ◽  
Author(s):  
Mark Kalisz ◽  
Edgar Bernardo ◽  
Anthony Beucher ◽  
Miguel Angel Maestro ◽  
Natalia del Pozo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Pancreatic Acinar Cells ◽  
Ductal Adenocarcinoma ◽  
Molecular Phenotype ◽  
Mesenchymal Transition ◽  
A Cell ◽  
Pancreatic Exocrine ◽  
Direct Genetic Evidence

AbstractDefects in transcriptional regulators of pancreatic exocrine differentiation have been implicated in pancreatic tumorigenesis, but the molecular mechanisms are poorly understood. The locus encoding the transcription factor HNF1A harbors susceptibility variants for pancreatic ductal adenocarcinoma (PDAC), while KDM6A, encoding the histone demethylase UTX, carries somatic mutations in PDAC. Here, we show that pancreas-specific Hnf1a null mutations phenocopy Utx deficient mutations, and both synergize with KrasG12D to cause PDAC with sarcomatoid features. We combine genetic, epigenomic and biochemical studies to show that HNF1A recruits UTX to genomic binding sites in pancreatic acinar cells. This remodels the acinar enhancer landscape, activates a differentiation program, and indirectly suppresses oncogenic and epithelial-mesenchymal transition genes. Finally, we identify a subset of non-classical PDAC samples that exhibit the HNF1A/UTX-deficient molecular phenotype. These findings provide direct genetic evidence that HNF1A-deficiency promotes PDAC. They also connect the tumor suppressive role of UTX deficiency with a cell-specific molecular mechanism that underlies PDAC subtype definition.

scholarly journals Role of Metabolic Reprogramming in Epithelial–Mesenchymal Transition (EMT)

2019 ◽  
Vol 20 (8) ◽  
pp. 2042 ◽  
Author(s):  
Hyunkoo Kang ◽  
Hyunwoo Kim ◽  
Sungmin Lee ◽  
HyeSook Youn ◽  
BuHyun Youn
Keyword(s):  
Tumor Progression ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metabolic Reprogramming ◽  
Metabolic Enzyme ◽  
Diverse Range ◽  
Mesenchymal Transition ◽  
Altered Glucose

Activation of epithelial–mesenchymal transition (EMT) is thought to be an essential step for cancer metastasis. Tumor cells undergo EMT in response to a diverse range of extra- and intracellular stimulants. Recently, it was reported that metabolic shifts control EMT progression and induce tumor aggressiveness. In this review, we summarize the involvement of altered glucose, lipid, and amino acid metabolic enzyme expression and the underlying molecular mechanisms in EMT induction in tumor cells. Moreover, we propose that metabolic regulation through gene-specific or pharmacological inhibition may suppress EMT and this treatment strategy may be applied to prevent tumor progression and improve anti-tumor therapeutic efficacy. This review presents evidence for the importance of metabolic changes in tumor progression and emphasizes the need for further studies to better understand tumor metabolism.

scholarly journals Long Non-Coding RNAs in Epithelial-Mesenchymal Transition of Pancreatic Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Kenji Takahashi ◽  
Kenzui Taniue ◽  
Yusuke Ono ◽  
Mikihiro Fujiya ◽  
Yusuke Mizukami ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Ductal Adenocarcinoma ◽  
Potential Contribution ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Invasion And Migration ◽  
Non Coding Rnas ◽  
And Migration

Non-coding RNAs (ncRNAs), or RNA molecules that do not code for proteins, are generally categorized as either small or long ncRNA (lncRNA) and are involved in the pathogenesis of several diseases including many cancers. Identification of a large number of ncRNAs could help to elucidate previously unknown mechanisms in phenotype regulation. Some ncRNAs are encapsulated by extracellular vesicles (EVs) and transferred to recipient cells to regulate cellular processes, including epigenetic and post-transcriptional regulations. Recent studies have uncovered novel molecular mechanisms and functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC), one of the most intractable cancers that is highly invasive and metastatic. As the epithelial-mesenchymal transition (EMT) triggers tumor cell invasion and migration, clarification of the roles of lncRNA in EMT and tumor cell stemness would be critical for improving diagnostic and therapeutic approaches in metastatic cancers. This review provides an overview of relevant studies on lncRNA and its involvement with EMT in PDAC. Emerging knowledge offers evidence for the dysregulated expression of lncRNAs and essential insights into the potential contribution of both lncRNAs and EVs in the pathogenesis of PDAC. Future directions and new clinical applications for PDAC are also discussed.

scholarly journals MiRNAs and LncRNAs: Dual Roles in TGF-β Signaling-Regulated Metastasis in Lung Cancer

2020 ◽  
Vol 21 (4) ◽  
pp. 1193 ◽  
Author(s):  
Xing-Ning Lai ◽  
Jun Li ◽  
Li-Bo Tang ◽  
Wen-Tong Chen ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Metastasis ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Circular Rnas ◽  
High Morbidity ◽  
Dual Roles ◽  
Mesenchymal Transition ◽  
Lung Cancer Metastasis ◽  
Non Coding Rnas

Lung cancer is one of the most malignant cancers around the world, with high morbidity and mortality. Metastasis is the leading cause of lung cancer deaths and treatment failure. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs), two groups of small non-coding RNAs (nc-RNAs), are confirmed to be lung cancer oncogenes or suppressors. Transforming growth factor-β (TGF-β) critically regulates lung cancer metastasis. In this review, we summarize the dual roles of miRNAs and lncRNAs in TGF-β signaling-regulated lung cancer epithelial-mesenchymal transition (EMT), invasion, migration, stemness, and metastasis. In addition, lncRNAs, competing endogenous RNAs (ceRNAs), and circular RNAs (circRNAs) can act as miRNA sponges to suppress miRNAs, thereby mediating TGF-β signaling-regulated lung cancer invasion, migration, and metastasis. Through this review, we hope to cast light on the regulatory mechanisms of miRNAs and lncRNAs in TGF-β signaling-regulated lung cancer metastasis and provide new insights for lung cancer treatment.

scholarly journals A long non-coding RNA lncRNA-PE promotes invasion and epithelial–mesenchymal transition in hepatocellular carcinoma through the miR-200a/b-ZEB1 pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770575 ◽  
Author(s):  
Yuan Shen ◽  
Shanshan Liu ◽  
Hanyu Yuan ◽  
Xiaomin Ying ◽  
Hanjiang Fu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
Hepatocellular Carcinoma Cells ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Non Coding Rnas ◽  
And Migration

Long non-coding RNAs have been revealed to play important roles in the progression of hepatocellular carcinoma. However, the detailed mechanisms underlying their activities are not fully understood. Using microarray technology, a number of long non-coding RNAs were previously identified to be aberrantly expressed in hepatocellular carcinoma. In this study, one of these long non-coding RNAs, designated lncRNA-PE (lncRNA promotes epithelial–mesenchymal transition), was further explored to study its expression profile and function. A cohort of human hepatocellular carcinoma tissue samples combined with benign controls and established human hepatocellular carcinoma cell lines were examined for the expression of lncRNA-PE. The biological functions of lncRNA-PE were examined by wound-healing and Transwell assays, which revealed that lncRNA-PE promotes cell invasion and migration. By detecting the level of epithelial–mesenchymal transition markers, lncRNA-PE was revealed to promote epithelial–mesenchymal transition in hepatocellular carcinoma cells. Further study suggested that lncRNA-PE downregulated miR-200a/b by repressing the primary transcript expression, enhanced ZEB1 expression, and promoted epithelial–mesenchymal transition of hepatocellular carcinoma cells. All these data imply that lncRNA-PE might play an important role in hepatocellular carcinoma development via the miR-200a/b-ZEB1 pathway.

scholarly journals Dynamics of Phenotypic Heterogeneity Associated with EMT and Stemness during Cancer Progression

2019 ◽  
Vol 8 (10) ◽  
pp. 1542 ◽  
Author(s):  
Mohit Kumar Jolly ◽  
Toni Celià-Terrassa
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Relevant Literature ◽  
Phenotypic Heterogeneity ◽  
State Transitions ◽  
Strong Impact ◽  
Mesenchymal Transition ◽  
Cancer Aggressiveness

Genetic and phenotypic heterogeneity contribute to the generation of diverse tumor cell populations, thus enhancing cancer aggressiveness and therapy resistance. Compared to genetic heterogeneity, a consequence of mutational events, phenotypic heterogeneity arises from dynamic, reversible cell state transitions in response to varying intracellular/extracellular signals. Such phenotypic plasticity enables rapid adaptive responses to various stressful conditions and can have a strong impact on cancer progression. Herein, we have reviewed relevant literature on mechanisms associated with dynamic phenotypic changes and cellular plasticity, such as epithelial–mesenchymal transition (EMT) and cancer stemness, which have been reported to facilitate cancer metastasis. We also discuss how non-cell-autonomous mechanisms such as cell–cell communication can lead to an emergent population-level response in tumors. The molecular mechanisms underlying the complexity of tumor systems are crucial for comprehending cancer progression, and may provide new avenues for designing therapeutic strategies.

RAMS11 Promotes CRC Through Mtor-Dependent Inhibition of Autophagy, Suppression of Apoptosis, and Promotion of Epithelial-Mesenchymal Transition

2021 ◽  
Author(s):  
Md Zahirul ISLAM KHAN ◽  
Helen Ka-Wai LAW
Keyword(s):  
Cell Lines ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Normal Cells ◽  
Mesenchymal Transition ◽  
Migration Assay ◽  
Diagnosis And Prognosis ◽  
Non Coding Rnas ◽  
And Migration

Abstract BackgroundLong non-coding RNAs (lncRNAs), a class of non-coding RNAs (ncRNAs) associated with diverse biological processes of cells. Over the past decades, cumulating research evidences revealed that abnormal expressions of lncRNAs are associated with colorectal cancer (CRC) initiation, progression, metastasis, and resistance to therapies. Moreover, their usefulness as candidate biomarkers for CRC diagnosis and prognosis are well evident throughout previous literature. In the current study, we examined the role and molecular mechanisms of newly identified lncRNA named RNA associated with metastasis-11 (RAMS11) in CRC development. MethodsThe expression of RAMS11 in CRC cell lines DLD-1, HT-29, HCT-116, and SW480 and colon normal cells CCD-112-CoN were evaluated by quantitative RT-qPCR. The results showed that the RAMS11 is significantly upregulated in CRC cell lines compared to the normal cells. The CCK-8 proliferation assay, colony formation assay, and migration assay were performed to evaluate the biological and physiological functions of RAMS11 in vitro. To decipher the molecular mechanisms of RAMS11 medicated CRC progression, we further performed western blot analysis of the key pathway proteins (e.g., AMPK, AKT, and mTOR).ResultsOur results revealed that higher expression of RAMS11 is associated with increased CRC proliferation, migration, and development of metastasis. Knockdown of RAMS11 induced autophagy, apoptosis along with reduction of epithelial-mesenchymal transition (EMT) suggesting that RAMS11 is involved in CRC progression. The molecular mechanisms of RAMS11 indicated that knockdown of RAMS11 significantly inhibited CRC carcinogenesis through mTOR-dependent autophagy induction. ConclusionsIn sum, our results suggested that RAMS11 is an important oncogene in CRC pathogenesis. Targeting RAMS11 could be a potential therapeutic strategy for CRC management.

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