The microRNA-200 family: still much to discover

2016 ◽  
Vol 7 (5-6) ◽  
pp. 311-319 ◽  
Author(s):  
Daniel Senfter ◽  
Sibylle Madlener ◽  
Georg Krupitza ◽  
Robert M. Mader
Keyword(s):  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Potential Role ◽  
Predictive Biomarker ◽  
Mesenchymal Transition ◽  
Cellular Processes ◽  
Active Regulation ◽  
The Individual ◽  
Open Issues

AbstractIn the last decade, microRNAs (miRs or miRNAs) became of great interest in cancer research due to their multifunctional and active regulation in a variety of vital cellular processes. In this review, we discuss the miR-200 family, which is composed of five members (miR-141, miR-200a/200b/200c and miR-429). Although being among the best investigated miRNAs in the field, there are still many open issues. Here, we describe the potential role of miR-200 as prognostic and/or predictive biomarker, its influence on motility and cell migration as well as its role in epithelial to mesenchymal transition (EMT) and metastasis formation in different tumour types. Recent studies also demonstrated the influence of miR-200 on drug resistance and described a correlation between miR-200 expression levels and overall survival of patients. Despite intense research in this field, the full role of the miR-200 family in cancer progression and metastasis is not completely understood and seems to differ between different tumour types and different cellular backgrounds. To elucidate these differences further, a finer characterisation of the role of the individual miRNA-200 family members is currently under investigation.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

The role of miR200c in leptin-mediated triple-negative breast cancer progression to an epithelial-to-mesenchymal transition.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12548-e12548
Author(s):  
Lucas Wang ◽  
Brittany Harlow ◽  
Laura Bowers ◽  
Stephen Hursting ◽  
Linda A deGraffenried ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Leptin Receptor ◽  
Triple Negative ◽  
Receptor Expression ◽  
Obese Women ◽  
Mesenchymal Transition

e12548 Background: Almost 40% of women with breast cancer are obese at diagnosis. Obesity is associated with a worse prognosis in triple negative breast cancer (TNBC). Preclinical studies have shown that leptin is an important factor associated with TNBC by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). Transcription factors SNAIL, TWIST and ZEB are critical components in enhancing EMT in cancer cells. The specific mechanism(s) by leptin regulates SNAIL, TWIST and ZEB expression remain unclear, limiting the development of effective interventions to improve outcomes in obese TNBC patients. Recent studies have demonstrated that miR200c, downstream of leptin receptor signaling, regulates the expression of SNAIL1, TWIST and ZEB. We will test the hypothesis that leptin contributes to obesity-induced EMT/CSC in TNBC through modulation of miR200c. Methods: Ob-R (leptin receptor) expression was suppressed in TNBC MDA-MB-231 and E-Wnt cells using shRNA (Ob-R null). Ob-R and Ob-R null cells were exposed to sera pooled from lean or obese women, as well as lean sera supplemented with leptin, after which expression of SNAIL, TWIST, ZEB and miR200c was measured by qPCR, while activation of the JAK-STAT pathway was assessed by Western blotting. Results: TNBC cells exposed to obese and high leptin conditions demonstrated increased expression of EMT markers compared to levels expressed under lean conditions. The Ob-R WT and null cells were used to determine the specific role of leptin signaling in regulating expression of SNAIL, TWIST and ZEB through miR200c. Conclusions: Both obese and high leptin conditions result in increased expression of EMT regulators, suggesting that effective targeting of this pathway may provide clinical benefit in the obese breast cancer patient. Elucidating the specific mediators of this pathway will guide development of novel and more potent medical therapies.

scholarly journals UNR/CSDE1 Expression Is Critical to Maintain Invasive Phenotype of Colorectal Cancer through Regulation of c-MYC and Epithelial-to-Mesenchymal Transition

2019 ◽  
Vol 8 (4) ◽  
pp. 560 ◽  
Author(s):  
Javier Martinez-Useros ◽  
Nuria Garcia-Carbonero ◽  
Weiyao Li ◽  
Maria J. Fernandez-Aceñero ◽  
Ion Cristobal ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Rna Binding ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Progression

CSDE1 (cold shock domain containing E1) gene is located upstream of the N-RAS locus, and codes for an RNA-binding protein named Upstream of N-Ras (UNR). In cancer, CSDE1 has been shown to regulate c-Fos, c-Myc, Pten, Rac1, or Vimentin. UNR/CSDE1 has been studied in breast, melanoma, pancreatic and prostate cancer. Then, the aim of this study is to evaluate the role of CSDE1/UNR in colorectal cancer progression and maintenance of aggressive phenotype. We firstly evaluated UNR/CSDE1 expression in human colon cancer derived cell lines and patient samples. Subsequently, we performed functional experiments by UNR/CSDE1 downregulation. We also evaluated UNR/CSDE1 prognostic relevance in two independent sets of patients. Not only was UNR/CSDE1 expression higher in tumor samples compared to untransformed samples, but also in colonospheres and metastatic origin cell lines than their parental and primary cell lines, respectively. Downregulation of UNR/CSDE1 reduced cell viability and migration throughout a restrain of epithelial-to-mesenchymal transition and increases sensitivity to apoptosis. Interestingly, high UNR/CSDE1 expression was associated with poor prognosis and correlated positively with c-MYC expression in colorectal cancer samples and cell lines. Here, we show for the first time compelling data reporting the oncogenic role of UNR/CSDE1 in human colorectal cancer.

scholarly journals The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4720
Author(s):  
Paris Jabeen Asif ◽  
Ciro Longobardi ◽  
Michael Hahne ◽  
Jan Paul Medema
Keyword(s):  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Cancer Invasion ◽  
Cancer Associated Fibroblasts ◽  
Targeted Therapeutics ◽  
Invasion And Metastasis ◽  
Mesenchymal Transition ◽  
Future Studies

Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cancer cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and therapy resistance. As metastasis is a main reason for cancer-related deaths, it is crucial to understand the role of CAFs in this process. Colorectal cancer (CRC) is a heterogeneous disease and lethality is especially common in a subtype of CRC with high stromal infiltration. A key component of stroma is cancer-associated fibroblasts (CAFs). To provide new perspectives for research on CAFs and CAF-targeted therapeutics, especially in CRC, we discuss the mechanisms, crosstalk, and functions involved in CAF-mediated cancer invasion, metastasis, and protection. This summary can serve as a framework for future studies elucidating these roles of CAFs.

scholarly journals Epithelial-to-Mesenchymal Transition in the Light of Plasticity and Hybrid E/M States

2021 ◽  
Vol 10 (11) ◽  
pp. 2403
Author(s):  
Laura Bornes ◽  
Guillaume Belthier ◽  
Jacco van Rheenen
Keyword(s):  
Wound Healing ◽  
Cell Adhesion ◽  
Basement Membrane ◽  
Cell Polarity ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Therapy Resistance ◽  
Mesenchymal Transition

Epithelial-to-mesenchymal transition (EMT) is a cellular program which leads to cells losing epithelial features, including cell polarity, cell–cell adhesion and attachment to the basement membrane, while gaining mesenchymal characteristics, such as invasive properties and stemness. This program is involved in embryogenesis, wound healing and cancer progression. Over the years, the role of EMT in cancer progression has been heavily debated, and the requirement of this process in metastasis even has been disputed. In this review, we discuss previous discrepancies in the light of recent findings on EMT, plasticity and hybrid E/M states. Moreover, we highlight various tumor microenvironmental cues and cell intrinsic signaling pathways that induce and sustain EMT programs, plasticity and hybrid E/M states. Lastly, we discuss how recent findings on plasticity, especially on those that enable cells to switch between hybrid E/M states, have changed our understanding on the role of EMT in cancer metastasis, stemness and therapy resistance.

Hypothesizing the potential role of melatonin in inhibiting epithelial to mesenchymal transition in oral squamous cell carcinoma

2020 ◽  
Vol 145 ◽  
pp. 110346
Author(s):  
Thodur Madapusi Balaji ◽  
Saranya Varadarajan ◽  
Raghunathan Jagannathan ◽  
A. Thirumal Raj ◽  
Lakshmi Priya Sridhar ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Potential Role ◽  
Mesenchymal Transition

scholarly journals Epithelial to Mesenchymal Transition in Patients with Pancreatic Ductal Adenocarcinoma: State-of-the-Art and Therapeutic Opportunities

2021 ◽  
Vol 14 (8) ◽  
pp. 740
Author(s):  
Julie Dardare ◽  
Andréa Witz ◽  
Jean-Louis Merlin ◽  
Agathe Bochnakian ◽  
Paul Toussaint ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
State Of The Art ◽  
Ductal Adenocarcinoma ◽  
Mesenchymal Transition ◽  
Late Stages

Pancreatic ductal adenocarcinoma (PDAC) is one of the malignancies with the worst prognosis despite a decade of efforts. Up to eighty percent of patients are managed at late stages with metastatic disease, in part due to a lack of diagnosis. The effectiveness of PDAC therapies is challenged by the early and widespread metastasis. Epithelial to mesenchymal transition (EMT) is a major driver of cancer progression and metastasis. This process allows cancer cells to gain invasive properties by switching their phenotype from epithelial to mesenchymal. The importance of EMT has been largely described in PDAC, and its importance is notably highlighted by the two major subtypes found in PDAC: the classical epithelial and the quasi-mesenchymal subtypes. Quasi-mesenchymal subtypes have been associated with a poorer prognosis. EMT has also been associated with resistance to treatments such as chemotherapy and immunotherapy. EMT is associated with several key molecular markers both epithelial and mesenchymal. Those markers might be helpful as a biomarker in PDAC diagnosis. EMT might becoming a key new target of interest for the treatment PDAC. In this review, we describe the role of EMT in PDAC, its contribution in diagnosis, in the orientation and treatment follow-up. We also discuss the putative role of EMT as a new therapeutic target in the management of PDAC.

scholarly journals Defining the Role of GLI/Hedgehog Signaling in Chemoresistance: Implications in Therapeutic Approaches

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4746
Author(s):  
Jian Yi Chai ◽  
Vaisnevee Sugumar ◽  
Ahmed F. Alshanon ◽  
Won Fen Wong ◽  
Shin Yee Fung ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cancer Progression ◽  
Hedgehog Signaling ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Treatment Strategies ◽  
Cancer Treatments ◽  
Mesenchymal Transition ◽  
Hh Signaling

Insight into cancer signaling pathways is vital in the development of new cancer treatments to improve treatment efficacy. A relatively new but essential developmental signaling pathway, namely Hedgehog (Hh), has recently emerged as a major mediator of cancer progression and chemoresistance. The evolutionary conserved Hh signaling pathway requires an in-depth understanding of the paradigm of Hh signaling transduction, which is fundamental to provide the necessary means for the design of novel tools for treating cancer related to aberrant Hh signaling. This review will focus substantially on the canonical Hh signaling and the treatment strategies employed in different studies, with special emphasis on the molecular mechanisms and combination treatment in regard to Hh inhibitors and chemotherapeutics. We discuss our views based on Hh signaling’s role in regulating DNA repair machinery, autophagy, tumor microenvironment, drug inactivation, transporters, epithelial-to-mesenchymal transition, and cancer stem cells to promote chemoresistance. The understanding of this Achilles’ Heel in cancer may improve the therapeutic outcome for cancer therapy.

Sign in / Sign up

Export Citation Format

Share Document