scholarly journals MicroRNA-Assisted Hormone Cell Signaling in Colorectal Cancer Resistance

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 39
Author(s):  
Crescenzo Massaro ◽  
Elham Safadeh ◽  
Giulia Sgueglia ◽  
Hendrik G. Stunnenberg ◽  
Lucia Altucci ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Therapy Resistance ◽  
Disease Recurrence ◽  
Hormone Signaling ◽  
Cancer Resistance ◽  
Comprehensive Overview ◽  
Substantial Progress

Despite substantial progress in cancer therapy, colorectal cancer (CRC) is still the third leading cause of cancer death worldwide, mainly due to the acquisition of resistance and disease recurrence in patients. Growing evidence indicates that deregulation of hormone signaling pathways and their cross-talk with other signaling cascades inside CRC cells may have an impact on therapy resistance. MicroRNAs (miRNAs) are small conserved non-coding RNAs thatfunction as negative regulators in many gene expression processes. Key studies have identified miRNA alterations in cancer progression and drug resistance. In this review, we provide a comprehensive overview and assessment of miRNAs role in hormone signaling pathways in CRC drug resistance and their potential as future targets for overcoming resistance to treatment.

scholarly journals MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1040 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Hui Li Ang ◽  
Ebrahim Rahmani Moghadam ◽  
Shima Mohammadi ◽  
Vahideh Zarrin ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Therapy ◽  
Signaling Pathways ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
The Impact

Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of epithelial-mesenchymal transition (EMT) mechanism, therefore reducing metastasis. Additionally, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression.

Preliminary Study Results Of Multiple Drug Resistance In Patients With Advanced Types Of Colorectal Cancer

2010 ◽  
Vol 1 ◽  
Author(s):  
S Navruzov ◽  
S Abdujapparov ◽  
D Pulatov ◽  
H Islamov ◽  
Sh Matniyazova ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Therapy Resistance ◽  
Multiple Drug ◽  
Complex Treatment ◽  
Oncogene Expression ◽  
Study Results ◽  
Preliminary Study ◽  
Definition Of

In the department of coloproctology of NORC MH RUz 17 patients with disseminated forms of colorectal cancer was made the study of oncogenes and complex treatment by 2 protocols using FOLFOX-4 regime and FOLFIRI regime. In second protocol there used 2 sessions of endolymphatical polychemotherapy FOLFOX-4 regime against EHF-hyperthermia. All patients were performed additional investigations directed to study the presence of multiple drug resistance in them where definition of р53, bcl-2 oncogene expression. In our observations we followed resistance to FOLFOX-4 scheme in 4 patients, and to FOLFIRI scheme in 2 cases. In our studies hyperexpression of oncoproteine  р53 was correlated with the effect of conducted therapy whereas hyperexpression of oncoproteine bcl-2 showed therapy resistance. 

scholarly journals Role of non-coding RNAs as novel biomarkers for detection of colorectal cancer progression through interaction with the cell signaling pathways

Gene ◽  
2020 ◽  
Vol 753 ◽  
pp. 144796 ◽  
Author(s):  
Mohadeseh Esmaeili ◽  
Maryam Keshani ◽  
Mehrdad Vakilian ◽  
Maryam Esmaeili ◽  
Maryam Peymani ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Novel Biomarkers ◽  
Non Coding Rnas ◽  
Colorectal Cancer Progression ◽  
Cell Signaling Pathways

scholarly journals CD44 in Ovarian Cancer Progression and Therapy Resistance—A Critical Role for STAT3

2020 ◽  
Vol 10 ◽  
Author(s):  
Antons Martincuks ◽  
Pei-Chuan Li ◽  
Qianqian Zhao ◽  
Chunyan Zhang ◽  
Yi-Jia Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Critical Role ◽  
Therapy Resistance ◽  
Disease Recurrence ◽  
Metabolic Reprogramming ◽  
Metastatic Progression ◽  
Stem Cell Maintenance ◽  
Current State ◽  
Promising Therapeutic Target

Despite significant progress in cancer therapy over the last decades, ovarian cancer remains the most lethal gynecologic malignancy worldwide with the five-year overall survival rate less than 30% due to frequent disease recurrence and chemoresistance. CD44 is a non-kinase transmembrane receptor that has been linked to cancer metastatic progression, cancer stem cell maintenance, and chemoresistance development via multiple mechanisms across many cancers, including ovarian, and represents a promising therapeutic target for ovarian cancer treatment. Moreover, CD44-mediated signaling interacts with other well-known pro-tumorigenic pathways and oncogenes during cancer development, such as signal transducer and activator of transcription 3 (STAT3). Given that both CD44 and STAT3 are strongly implicated in the metastatic progression and chemoresistance of ovarian tumors, this review summarizes currently available evidence about functional crosstalk between CD44 and STAT3 in human malignancies with an emphasis on ovarian cancer. In addition to the role of tumor cell-intrinsic CD44 and STAT3 interaction in driving cancer progression and metastasis, we discuss how CD44 and STAT3 support the pro-tumorigenic tumor microenvironment and promote tumor angiogenesis, immunosuppression, and cancer metabolic reprogramming in favor of cancer progression. Finally, we review the current state of therapeutic CD44 targeting and propose superior treatment possibilities for ovarian cancer.

Roles of signaling pathways in drug resistance, cancer initiating cells and cancer progression and metastasis

2015 ◽  
Vol 57 ◽  
pp. 75-101 ◽  
Author(s):  
James A. McCubrey ◽  
Stephen L. Abrams ◽  
Timothy L. Fitzgerald ◽  
Lucio Cocco ◽  
Alberto M. Martelli ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Signaling Pathways ◽  
Cancer Progression

scholarly journals LncRNA BLACAT1/miR-519d-3p/CREB1 Axis Mediates Proliferation, Apoptosis, Migration, Invasion, and Drug-Resistance in Colorectal Cancer Progression

2020 ◽  
Vol Volume 12 ◽  
pp. 13137-13148
Author(s):  
Rui Chen ◽  
Shenkang Zhou ◽  
Jianhui Chen ◽  
Senbin Lin ◽  
Feifei Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Colorectal Cancer Progression

scholarly journals ECHS1, an interacting protein of LASP1, induces sphingolipid-metabolism imbalance to promote colorectal cancer progression by regulating ceramide glycosylation

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Rui Li ◽  
Yanyu Hao ◽  
Qiuhan Wang ◽  
Yuan Meng ◽  
Kunhe Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Specific Inhibitor ◽  
Sphingolipid Metabolism ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Interacting Protein

AbstractSphingolipid metabolic dysregulation has increasingly been considered to be a drug-resistance mechanism for a variety of tumors. In this study, through an LC–MS assay, LIM and SH3 protein 1 (LASP1) was identified as a sphingolipid-metabolism-involved protein, and short-chain enoyl-CoA hydratase (ECHS1) was identified as a new LASP1-interacting protein through a protein assay in colorectal cancer (CRC). Gain- and loss-of-function analyses demonstrated the stimulatory role played by ECHS1 in CRC cell proliferation, migration, and invasion in vitro and in vivo. Mechanistic studies of the underlying tumor-supportive oncometabolism indicate that ECHS1 enables altering ceramide (Cer) metabolism that increases glycosphingolipid synthesis (HexCer) by promoting UDP-glucose ceramide glycosyltransferase (UGCG). Further analysis showed that ECHS1 promotes CRC progression and drug resistance by releasing reactive oxygen species (ROS) and interfering mitochondrial membrane potential via the PI3K/Akt/mTOR-dependent signaling pathway. Meanwhile, the phenomenon of promoting the survival and drug resistance of CRC cells caused by ECHS1 could be reversed by Eliglustat, a specific inhibitor of UCCG, in vitro and in vivo. IHC assay showed that ECHS1 was overexpressed in CRC tissues, which was related to the differentiation and poor prognosis of CRC patients. This study provides new insight into the mechanism by which phospholipids promote drug resistance in CRC and identifies potential targets for future therapies.

Analysis of oxaliplatin resistance in colorectal cancer cells by combined proteomics and phosphoproteomic

2020 ◽  
Vol 17 ◽  
Author(s):  
Rui Yang ◽  
Kunli Feng ◽  
Yanhong Cao ◽  
Hao Wang ◽  
Baolong Wang
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Protein Domain ◽  
Cancer Resistance ◽  
Kegg Pathways ◽  
Colorectal Cancer Cells ◽  
Hplc Fractionation ◽  
Hct116 Cells

Background: Oxaliplatin(Oxa) is a major chemotherapy drug for colorectal cancer. However, drug resistance is a major cause of treatment failure for late-stage colorectal cancer. Therefore, it is necessary to explore the mechanism of resistance to oxaliplatin in HCT116 colorectal cancer cells. Objective: Therefore, this study explored the mechanisms of HCT116 cells resistance to oxaliplatin by combining the results of proteomic and phosphoproteomic analyses. Method: In this study, first，we constructed oxaliplatin-resistant HCT116 cells, called HCT116/Oxa. Then, we conducted a quantitative study of phosphoproteomics in HCT116 and HCT116/Oxa cells via TMT labeling, bio-material-based PTM enrichment, HPLC fractionation, and LC-MS/MS analyses. At the same time, we applied TMT/iTRAQ labeling, HPLC fractionation, and LC-MS/MS to conduct proteomic and phosphoproteomic analyses of the cell lines. Finally, we analyzed the results from Gene Ontology (GO), protein domain, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using the 1.5 change rate as a meaningful change threshold. Results: Our analysis confirmed the previously described mechanisms of colon cancer resistance and revealed the important role of phosphorylation in drug resistance. Conclusion: Collectively, this study provides a new direction for the study of oxaliplatin resistance in colorectal cancer.

scholarly journals Natural podophyllotoxin analog 4DPG attenuates EMT and colorectal cancer progression via activation of checkpoint kinase 2

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Archana Katoch ◽  
Debasis Nayak ◽  
Mir Mohd. Faheem ◽  
Aviral Kumar ◽  
Promod Kumar Sahu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Dependent Manner ◽  
Checkpoint Kinase ◽  
Mesenchymal Transition ◽  
Checkpoint Kinase 2 ◽  
Clinical Benefits ◽  
Colorectal Cancer Progression

AbstractEpithelial–mesenchymal transition (EMT) is critical for the metastatic dissemination of cancer cells and contributes to drug resistance. In this study, we observed that epithelial colorectal cancer (CRC) cells transiently exposed to 5-fluorouracil (5-FU) (a chemotherapeutic drug for CRC) as well as 5-FU-resistant cells (5-FU-R) develop EMT characters as evidenced by activation of Vimentin and augmented invasive properties. On the other hand, 4DPG (4′-demethyl-deoxypodophyllotoxin glucoside), a natural podophyllotoxin analog attenuates EMT and invadopodia formation abilities of HCT-116/5-FU-R and SW-620/5-FU-R cells. Treatment with 4DPG restrains Vimentin phosphorylation (Ser38) in 5-FU-R cells, along with downregulation of mesenchymal markers Twist1 and MMP-2 while augmenting the expression of epithelial markers E-cadherin and TIMP-1. Moreover, 4DPG boosts the tumor-suppressor protein, checkpoint kinase 2 (Chk2) via phosphorylation at Thr68 in a dose-dependent manner in 5-FU-R cells. Mechanistically, SiRNA-mediated silencing of Chk2, as well as treatment with Chk2-specific small-molecule inhibitor (PV1019), divulges that 4DPG represses Vimentin activation in a Chk2-dependent manner. Furthermore, immunoprecipitation analysis unveiled that 4DPG prevents complex formation between Vimentin and p53 resulting in the rescue of p53 and its nuclear localization in aggressive 5-FU-R cells. In addition, 4DPG confers suitable pharmacokinetic properties and strongly abrogates tumor growth, polyps formation, and lung metastasis in an orthotopic rat colorectal carcinoma model. In conclusion, our findings demonstrate 4DPG as a targeted antitumor/anti-metastatic pharmacological lead compound to circumvent EMT-associated drug resistance and suggest its clinical benefits for the treatment of aggressive cancers.

scholarly journals Association of the Epithelial–Mesenchymal Transition (EMT) with Cisplatin Resistance

2020 ◽  
Vol 21 (11) ◽  
pp. 4002 ◽  
Author(s):  
Milad Ashrafizadeh ◽  
Ali Zarrabi ◽  
Kiavash Hushmandi ◽  
Mahshad Kalantari ◽  
Reza Mohammadinejad ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Therapy Resistance ◽  
Nuclear Factor Κb ◽  
Molecular Pathways ◽  
Cancer Resistance ◽  
Mesenchymal Transition ◽  
The Impact

Therapy resistance is a characteristic of cancer cells that significantly reduces the effectiveness of drugs. Despite the popularity of cisplatin (CP) as a chemotherapeutic agent, which is widely used in the treatment of various types of cancer, resistance of cancer cells to CP chemotherapy has been extensively observed. Among various reported mechanism(s), the epithelial–mesenchymal transition (EMT) process can significantly contribute to chemoresistance by converting the motionless epithelial cells into mobile mesenchymal cells and altering cell–cell adhesion as well as the cellular extracellular matrix, leading to invasion of tumor cells. By analyzing the impact of the different molecular pathways such as microRNAs, long non-coding RNAs, nuclear factor-κB (NF-ĸB), phosphoinositide 3-kinase-related protein kinase (PI3K)/Akt, mammalian target rapamycin (mTOR), and Wnt, which play an important role in resistance exhibited to CP therapy, we first give an introduction about the EMT mechanism and its role in drug resistance. We then focus specifically on the molecular pathways involved in drug resistance and the pharmacological strategies that can be used to mitigate this resistance. Overall, we highlight the various targeted signaling pathways that could be considered in future studies to pave the way for the inhibition of EMT-mediated resistance displayed by tumor cells in response to CP exposure.

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