scholarly journals RhoGTPase Signalling in Cancer Progression and Dissemination

2021 ◽  
Author(s):  
Eva Crosas-Molist ◽  
Remi Samain ◽  
Leonie Kohlhammer ◽  
Jose Orgaz ◽  
Samantha George ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Tumour Microenvironment ◽  
Normal Tissues ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
Metastatic Process ◽  
Tumour Initiation

Rho GTPases are a family of small G proteins that regulate a wide array of cellular processes related to their key roles controlling the cytoskeleton. On the other hand, cancer is a multi-step disease caused by the accumulation of genetic mutations and epigenetic alterations, from the initial stages of cancer development when cells in normal tissues undergo transformation, to the acquisition of invasive and metastatic traits, responsible for a large number of cancer related deaths. In this review, we discuss the role of Rho GTPase signalling in cancer in every step of disease progression. Rho GTPases contribute to tumour initiation and progression, by regulating proliferation and apoptosis, but also metabolism, senescence and cell stemness. Rho GTPases play a major role in cell migration, and in the metastatic process. They are also involved in interactions with the tumour microenvironment and regulate inflammation, contributing to cancer progression. After years of intensive research, we highlight the importance of relevant models in the Rho GTPase field, and we reflect on the therapeutic opportunities arising for cancer patients.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals RHO GTPase-Related Long Noncoding RNAs in Human Cancers

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5386
Author(s):  
Mahsa Saliani ◽  
Amin Mirzaiebadizi ◽  
Niloufar Mosaddeghzadeh ◽  
Mohammad Reza Ahmadian
Keyword(s):  
Signaling Pathways ◽  
Cancer Progression ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Cell Types ◽  
Critical Signal ◽  
Aberrant Expression ◽  
Cellular Processes ◽  
And Migration

RHO GTPases are critical signal transducers that regulate cell adhesion, polarity, and migration through multiple signaling pathways. While all these cellular processes are crucial for the maintenance of normal cell homeostasis, disturbances in RHO GTPase-associated signaling pathways contribute to different human diseases, including many malignancies. Several members of the RHO GTPase family are frequently upregulated in human tumors. Abnormal gene regulation confirms the pivotal role of lncRNAs as critical gene regulators, and thus, they could potentially act as oncogenes or tumor suppressors. lncRNAs most likely act as sponges for miRNAs, which are known to be dysregulated in various cancers. In this regard, the significant role of miRNAs targeting RHO GTPases supports the view that the aberrant expression of lncRNAs may reciprocally change the intensity of RHO GTPase-associated signaling pathways. In this review article, we summarize recent advances in lncRNA research, with a specific focus on their sponge effects on RHO GTPase-targeting miRNAs to crucially mediate gene expression in different cancer cell types and tissues. We will focus in particular on five members of the RHO GTPase family, including RHOA, RHOB, RHOC, RAC1, and CDC42, to illustrate the role of lncRNAs in cancer progression. A deeper understanding of the widespread dysregulation of lncRNAs is of fundamental importance for confirmation of their contribution to RHO GTPase-dependent carcinogenesis.

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.

scholarly journals Role of Glutathione in Cancer Progression and Chemoresistance

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nicola Traverso ◽  
Roberta Ricciarelli ◽  
Mariapaola Nitti ◽  
Barbara Marengo ◽  
Anna Lisa Furfaro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Differentiation ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Cytotoxic Effects ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
Glutathione Disulphide ◽  
Increased Susceptibility

Glutathione (GSH) plays an important role in a multitude of cellular processes, including cell differentiation, proliferation, and apoptosis, and disturbances in GSH homeostasis are involved in the etiology and progression of many human diseases including cancer. While GSH deficiency, or a decrease in the GSH/glutathione disulphide (GSSG) ratio, leads to an increased susceptibility to oxidative stress implicated in the progression of cancer, elevated GSH levels increase the antioxidant capacity and the resistance to oxidative stress as observed in many cancer cells. The present review highlights the role of GSH and related cytoprotective effects in the susceptibility to carcinogenesis and in the sensitivity of tumors to the cytotoxic effects of anticancer agents.

scholarly journals Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA

Oncogenesis ◽  
2020 ◽  
Vol 9 (9) ◽  
Author(s):  
Guofang Chen ◽  
Binya Liu ◽  
Shasha Yin ◽  
Shuangdi Li ◽  
Yu’e Guo ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cancer Progression ◽  
Critical Role ◽  
Tumour Microenvironment ◽  
Cell Phenotype ◽  
Mrna Levels ◽  
Hypoxic Conditions ◽  
Inducing Factors ◽  
Tumour Initiation

Abstract Endometrial cancer stem cells (ECSCs) are stem-like cells endowed with self-renewal and differentiation abilities, and these cells are essential for cancer progression in endometrial cancer (EC). As hallmarks of the tumour microenvironment (TME), hypoxia and hypoxia-inducing factors (HIFs) give rise to the dysregulation of tumour stemness genes, such as SOX2. Against this backdrop, we investigated the regulatory mechanisms regulated by HIFs and SOX2 in ECSCs during EC development. Here, ECSCs isolated from EC cell lines and tissues were found to express stemness genes (CD133 and aldehyde dehydrogenase, ALDH1) following the induction of their ECSC expansion. Notably, m6A methylation of RNA and HIF-1α/2α-dependent AlkB homologue 5 (ALKBH5) participate in the regulation of HIFs and SOX2 in EC, as confirmed by the observations that mRNA levels of m6A demethylases and ALKBH5 significantly increase under hypoxic conditions in ECSCs. Moreover, hypoxia and high ALKBH5 levels restore the stem-like state of differentiated ECSCs and increase the ECSC-like phenotype, whereas the knockdown of HIFs or ALKBH5 significantly reduces their tumour initiation capacity. In addition, our findings validate the role of ALKBH5 in promoting SOX2 transcription via mRNA demethylation, thereby maintaining the stem-like state and tumorigenicity potential of ECSCs. In conclusion, these observations demonstrate a critical role for m6A methylation-mediated regulation of the HIF-ALKBH5-SOX2 axis during ECSC expansion in hypoxic TMEs.

scholarly journals LncRNA EGOT regulates the proliferation and apoptosis of colorectal cancer by miR-33b-5p/CROT axis

2020 ◽  
Author(s):  
Yin Ni ◽  
Chunbo Li ◽  
Chen Bo ◽  
Bomiao Zhang ◽  
Yanlong Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Noncoding Rnas ◽  
Poor Overall Survival ◽  
Downstream Target ◽  
Cellular Processes ◽  
Functional Assays ◽  
Proliferation And Apoptosis ◽  
Detailed Function

Accumulating researches have proved that long noncoding RNAs (lncRNAs) regulate a variety of cellular processes during cancer progression. However, the detailed function of most lncRNAs in colorectal cancer (CRC) remains mostly unknown. This study was aimed at exploring the specific role of lncRNA EGOT in CRC. Data from this study revealed that EGOT expression was obviously upregulated in CRC tissues and cell lines, and high EGOT expression indicated poor overall survival of CRC patients. Besides, functional assays proved that EGOT knockdown inhibited cell proliferation and promoted cell apoptosis in CRC. Then, subsequent molecular mechanism assays uncovered that EGOT could bind with miR-33b-5p and negatively regulate miR-33b-5p expression. Additionally, CROT was a downstream target of miR-33b-5p. Further, rescued-function assays suggested that the suppressive influence of EGOT depletion on CRC progression was reversed by miR-33b-5p inhibition or CROT overexpression. In conclusion, lncRNA EGOT mediates the tumor-facilitating part in CRC via miR-33b-5p/CROT pathway.

scholarly journals Role of the NUDT Enzymes in Breast Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2267
Author(s):  
Roni H. G. Wright ◽  
Miguel Beato
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Breast Cancers ◽  
Metastatic Colonization ◽  
Hormone Receptor Positive ◽  
Aggressive Cancer ◽  
Cancer Types ◽  
Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

scholarly journals Tumor-suppressive and tumor-promoting role of Tgf-Beta in Hepatocellular Carcinoma

2016 ◽  
Vol 9 (1) ◽  
pp. 41 ◽  
Author(s):  
Somyoth Sridurongrit
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Tumor Development ◽  
The Other ◽  
Tgf Beta ◽  
Hepatic Cells ◽  
Proliferation And Apoptosis ◽  
Regulation Of Proliferation ◽  
Metastatic Process

Tgf-Beta is a pleiotropic cytokine with diverse functions on hepatic cells. The well-known function of Tgf-Beta in pathogenesis of liver disease is to stimulate liver fibrosis that often precedes the onset of liver cancer. While Tgf-Beta-mediated fibrosis seems to make liver more prone to the development of liver cancer, Tgf-Beta suppresses initial malignant transformation of hepatic cells thru regulation of proliferation and apoptosis. On the other hand, Tgf-Beta has shown to act as an inducer of tumor development thru enhancement of metastatic process. Additionally, it has been shown that Tgf-Beta signaling in hepatocytes promotes hepatocarcinogenesis caused by certain genetic conditions. This review highlights observations that have improved an understanding of how Tgf-Beta contributes to the development of hepatocellular carcinoma.

scholarly journals A control engineering approach to understanding the TGF-β paradox in cancer

2011 ◽  
Vol 9 (71) ◽  
pp. 1389-1397 ◽  
Author(s):  
Seung-Wook Chung ◽  
Carlton R. Cooper ◽  
Mary C. Farach-Carson ◽  
Babatunde A. Ogunnaike
Keyword(s):  
Cancer Cells ◽  
Mechanistic Model ◽  
Tumour Suppressor ◽  
Cancer Tissue ◽  
Control Engineering ◽  
Cellular Processes ◽  
Proliferation And Apoptosis ◽  
High Level ◽  
Quantitative Explanation

TGF-β, a key cytokine that regulates diverse cellular processes, including proliferation and apoptosis, appears to function paradoxically as a tumour suppressor in normal cells, and as a tumour promoter in cancer cells, but the mechanisms underlying such contradictory roles remain unknown. In particular, given that this cytokine is primarily a tumour suppressor, the conundrum of the unusually high level of TGF-β observed in the primary cancer tissue and blood samples of cancer patients with the worst prognosis, remains unresolved. To provide a quantitative explanation of these paradoxical observations, we present, from a control theory perspective, a mechanistic model of TGF-β-driven regulation of cell homeostasis. Analysis of the overall system model yields quantitative insight into how cell population is regulated, enabling us to propose a plausible explanation for the paradox: with the tumour suppressor role of TGF-β unchanged from normal to cancer cells, we demonstrate that the observed increased level of TGF-β is an effect of cancer cell phenotypic progression (specifically, acquired TGF-β resistance), not the cause . We are thus able to explain precisely why the clinically observed correlation between elevated TGF-β levels and poor prognosis is in fact consistent with TGF-β's original (and unchanged) role as a tumour suppressor.

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