scholarly journals Molecular Mechanism of Stem Cell Differentiation into Adipocytes and Adipocyte Differentiation of Malignant Tumor

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Kexin Zhang ◽  
Xudong Yang ◽  
Qi Zhao ◽  
Zugui Li ◽  
Fangmei Fu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Adult Stem Cells ◽  
Molecular Mechanisms ◽  
Stem Cell Differentiation ◽  
Signal Pathways ◽  
High Plasticity ◽  
Mesenchymal Transition ◽  
Adipose Differentiation

Adipogenesis is the process through which preadipocytes differentiate into adipocytes. During this process, the preadipocytes cease to proliferate, begin to accumulate lipid droplets, and develop morphologic and biochemical characteristics of mature adipocytes. Mesenchymal stem cells (MSCs) are a type of adult stem cells known for their high plasticity and capacity to generate mesodermal and nonmesodermal tissues. Many mature cell types can be generated from MSCs, including adipocyte, osteocyte, and chondrocyte. The differentiation of stem cells into multiple mature phenotypes is at the basis for tissue regeneration and repair. Cancer stem cells (CSCs) play a very important role in tumor development and have the potential to differentiate into multiple cell lineages. Accumulating evidence has shown that cancer cells can be induced to differentiate into various benign cells, such as adipocytes, fibrocytes, osteoblast, by a variety of small molecular compounds, which may provide new strategies for cancer treatment. Recent studies have reported that tumor cells undergoing epithelial-to-mesenchymal transition can be induced to differentiate into adipocytes. In this review, molecular mechanisms, signal pathways, and the roles of various biological processes in adipose differentiation are summarized. Understanding the molecular mechanism of adipogenesis and adipose differentiation of cancer cells may contribute to cancer treatments that involve inducing differentiation into benign cells.

scholarly journals Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers, Signaling Pathways and miRNAome

2021 ◽  
Vol 22 (4) ◽  
pp. 1603
Author(s):  
Andrea Angius ◽  
Antonio Mario Scanu ◽  
Caterina Arru ◽  
Maria Rosaria Muroni ◽  
Vincenzo Rallo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Predictive Biomarkers ◽  
Small Cells ◽  
Signal Pathways ◽  
Mesenchymal Transition

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.

scholarly journals Cancer Stemness: p53 at the Wheel

2021 ◽  
Vol 10 ◽  
Author(s):  
Dishari Ghatak ◽  
Damayanti Das Ghosh ◽  
Susanta Roychoudhury
Keyword(s):  
Stem Cells ◽  
Cancer Cells ◽  
Adult Stem Cells ◽  
Critical Role ◽  
Mutant P53 ◽  
Gain Of Function ◽  
Cancer Stemness ◽  
Self Renewal ◽  
Mesenchymal Transition

The tumor suppressor p53 maintains an equilibrium between self-renewal and differentiation to sustain a limited repertoire of stem cells for proper development and maintenance of tissue homeostasis. Inactivation of p53 disrupts this balance and promotes pluripotency and somatic cell reprogramming. A few reports in recent years have indicated that prevalent TP53 oncogenic gain-of-function (GOF) mutations further boosts the stemness properties of cancer cells. In this review, we discuss the role of wild type p53 in regulating pluripotency of normal stem cells and various mechanisms that control the balance between self-renewal and differentiation in embryonic and adult stem cells. We also highlight how inactivating and GOF mutations in p53 stimulate stemness in cancer cells. Further, we have explored the various mechanisms of mutant p53-driven cancer stemness, particularly emphasizing on the non-coding RNA mediated epigenetic regulation. We have also analyzed the association of cancer stemness with other crucial gain-of-function properties of mutant p53 such as epithelial to mesenchymal transition phenotypes and chemoresistance to understand how activation of one affects the other. Given the critical role of cancer stem-like cells in tumor maintenance, cancer progression, and therapy resistance of mutant p53 tumors, targeting them might improve therapeutic efficacy in human cancers with TP53 mutations.

scholarly journals New Insights into Osteogenic and Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells and Their Potential Clinical Applications for Bone Regeneration in Pediatric Orthopaedics

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Nicola Giuliani ◽  
Gina Lisignoli ◽  
Marina Magnani ◽  
Costantina Racano ◽  
Marina Bolzoni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Chondrogenic Differentiation ◽  
Adult Stem Cells ◽  
Molecular Mechanisms ◽  
Human Mesenchymal Stem Cells ◽  
Signal Pathways

Human mesenchymal stem cells (hMSCs) are pluripotent adult stem cells capable of being differentiated into osteoblasts, adipocytes, and chondrocytes. The osteogenic differentiation of hMSCs is regulated either by systemic hormones or by local growth factors able to induce specific intracellular signal pathways that modify the expression and activity of several transcription factors. Runt-related transcription factor 2 (Runx2) and Wnt signaling-related molecules are the major factors critically involved in the osteogenic differentiation process by hMSCs, and SRY-related high-mobility-group (HMG) box transcription factor 9 (SOX9) is involved in the chondrogenic one. hMSCs have generated a great interest in the field of regenerative medicine, particularly in bone regeneration. In this paper, we focused our attention on the molecular mechanisms involved in osteogenic and chondrogenic differentiation of hMSC, and the potential clinical use of hMSCs in osteoarticular pediatric disease characterized by fracture nonunion and pseudarthrosis.

Biological Aspects and Clinical Applications of Mesenchymal Stem Cells: Key Features You Need to be Aware of.

2020 ◽  
Vol 21 ◽  
Author(s):  
Mohammad Saeedi ◽  
Muhammad Sadeqi Nezhad ◽  
Fatemeh Mehranfar ◽  
Mahdieh Golpour ◽  
Mohammad Ali Esakandari ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Immune Modulation ◽  
Adult Stem Cells ◽  
Inflammatory Diseases ◽  
High Capacity ◽  
Genetically Engineered ◽  
Cartilage Cells ◽  
Biological Aspects

: Mesenchymal stem cells (MSCs), a form of adult stem cells, are known to have a self-renewing property and the potential to specialize into a multitude of cells and tissues such as adipocytes, cartilage cells, and fibroblasts. MSCs can migrate and home to the desired target zone where inflammation is present. The unique characteristics of MSCs in repairing, differentiation, regeneration, and its high capacity of immune modulation has attracted tremendous attention for exerting them in clinical purposes, as they contribute to tissue regeneration process and anti-tumor activity. The MSCs-based treatment has demonstrated remarkable applicability towards various diseases such as heart and bone malignancies, and cancer cells. Importantly, genetically engineered MSCs, as a state-of-the-art therapeutic approach, could address some clinical hurdles by systemic secretion of cytokines and other agents with a short half-life and high toxicity. Therefore, understanding the biological aspects and the characteristics of MSCs is an imperative issue of concern. Herein, we provide an overview of the therapeutic application and the biological features of MSCs against different inflammatory diseases and cancer cells. We further shed light on MSCs physiological interaction, such as migration, homing, and tissue repairing mechanisms with different healthy and inflamed tissues.

scholarly journals MicroRNAs and Stem-like Properties: The Complex Regulation Underlying Stemness Maintenance and Cancer Development

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1074
Author(s):  
Giuseppina Divisato ◽  
Silvia Piscitelli ◽  
Mariantonietta Elia ◽  
Emanuela Cascone ◽  
Silvia Parisi
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Embryonic Stem ◽  
Cell Types ◽  
Cancer Development ◽  
Special Focus ◽  
Self Renewal ◽  
Mesenchymal Transition ◽  
Different Cell Types

Embryonic stem cells (ESCs) have the extraordinary properties to indefinitely proliferate and self-renew in culture to produce different cell progeny through differentiation. This latter process recapitulates embryonic development and requires rounds of the epithelial–mesenchymal transition (EMT). EMT is characterized by the loss of the epithelial features and the acquisition of the typical phenotype of the mesenchymal cells. In pathological conditions, EMT can confer stemness or stem-like phenotypes, playing a role in the tumorigenic process. Cancer stem cells (CSCs) represent a subpopulation, found in the tumor tissues, with stem-like properties such as uncontrolled proliferation, self-renewal, and ability to differentiate into different cell types. ESCs and CSCs share numerous features (pluripotency, self-renewal, expression of stemness genes, and acquisition of epithelial–mesenchymal features), and most of them are under the control of microRNAs (miRNAs). These small molecules have relevant roles during both embryogenesis and cancer development. The aim of this review was to recapitulate molecular mechanisms shared by ESCs and CSCs, with a special focus on the recently identified classes of microRNAs (noncanonical miRNAs, mirtrons, isomiRs, and competitive endogenous miRNAs) and their complex functions during embryogenesis and cancer development.

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

scholarly journals Functional antagonism of chromatin modulators regulates epithelial-mesenchymal transition

2021 ◽  
Vol 7 (9) ◽  
pp. eabd7974
Author(s):  
Michela Serresi ◽  
Sonia Kertalli ◽  
Lifei Li ◽  
Matthias Jürgen Schmitt ◽  
Yuliia Dramaretska ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Transcriptional Control ◽  
Molecular Mechanisms ◽  
Developmental Process ◽  
Epithelial Mesenchymal Transition ◽  
Chromatin Remodelers ◽  
Mesenchymal Transition ◽  
Signature Genes ◽  
Chromatin Regulators ◽  
The Impact

Epithelial-mesenchymal transition (EMT) is a developmental process hijacked by cancer cells to modulate proliferation, migration, and stress response. Whereas kinase signaling is believed to be an EMT driver, the molecular mechanisms underlying epithelial-mesenchymal interconversion are incompletely understood. Here, we show that the impact of chromatin regulators on EMT interconversion is broader than that of kinases. By combining pharmacological modulation of EMT, synthetic genetic tracing, and CRISPR interference screens, we uncovered a minority of kinases and several chromatin remodelers, writers, and readers governing homeostatic EMT in lung cancer cells. Loss of ARID1A, DOT1L, BRD2, and ZMYND8 had nondeterministic and sometimes opposite consequences on epithelial-mesenchymal interconversion. Together with RNAPII and AP-1, these antagonistic gatekeepers control chromatin of active enhancers, including pan-cancer-EMT signature genes enabling supraclassification of anatomically diverse tumors. Thus, our data uncover general principles underlying transcriptional control of cancer cell plasticity and offer a platform to systematically explore chromatin regulators in tumor-state–specific therapy.

scholarly journals Area light source‐triggered latent angiogenic molecular mechanisms intensify therapeutic efficacy of adult stem cells

2021 ◽  
Author(s):  
Yu‐Jin Kim ◽  
Sung‐Won Kim ◽  
Gwang‐Bum Im ◽  
Yeong Hwan Kim ◽  
Gun‐Jae Jeong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Light Source ◽  
Therapeutic Efficacy ◽  
Adult Stem Cells ◽  
Molecular Mechanisms

scholarly journals PRMT5 Promotes EMT Through Regulating Akt Activity in Human Lung Cancer

2021 ◽  
Vol 30 ◽  
pp. 096368972110017
Author(s):  
Jianhao Huang ◽  
Yonghua Zheng ◽  
Xiao Zheng ◽  
Bao Qian ◽  
Qi Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Lung ◽  
Akt Signaling ◽  
Lung Cancer Cells ◽  
Signaling Cascades ◽  
Human Lung Cancer ◽  
Mesenchymal Transition ◽  
Human Lung Cancer Cells

The type II protein arginine methyltransferase 5 (PRMT5) has been engaged in various human cancer development and progression types. Nevertheless, few studies uncover the biological functions of PRMT5 in the epithelial-mesenchymal transition (EMT) of human lung cancer cells, and the associated molecular mechanisms and signaling cascades are entirely unknown. Here, we show that PRMT5 is the ectopic expression in human lung cancer tissues and cell lines. Further study reveals that silencing PRMT5 by lentivirus-mediated shRNA or blocking of PRMT5 by specific inhibitor GSK591 attenuates the expression levels of EMT-related markers in vivo, using the xenograft mouse model. Moreover, our results show that down-regulation of PRMT5 impairs EGFR/Akt signaling cascades in human lung cancer cells, whereas re-expression of PRMT5 recovers those changes, suggesting that PRMT5 regulates EMT probably through EGFR/Akt signaling axis. Altogether, our results demonstrate that PRMT5 serves as a critical oncogenic regulator and promotes EMT in human lung cancer cells. More importantly, our findings also suggest that PRMT5 may be a potential therapeutic candidate for the treatment of human lung cancer.

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