DUSP10 Is a Regulator of YAP1 Activity Promoting Cell Proliferation and Colorectal Cancer Progression

Jiménez-Martínez, Marta; Ostalé, Cristina M.; Burg, Lennart R. van der; Galán-Martínez, Javier; Hardwick, James C.H.; López‐Pérez, Ricardo; Hawinkels, Lukas J.A.C.; Stamatakis, Konstantinos; Fresno, Manuel

doi:10.3390/cancers11111767

Cited by 10 publications

(15 citation statements)

References 40 publications

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“…Interestingly, PGF2a through FP receptors can upregulate the expression of CYR61 mRNA (Xu et al, 2009). We also found a significant positive correlation of COX2, DUSP10 with CYR61 in colon carcinoma cell lines (Jimenez-Martinez et al, 2019a).…”

Section: Cox-2 and The Tgf-b Pathwaysupporting

confidence: 59%

“…Additionally, the quantity of nuclear DUSP10 in CRC tumor biopsies is directly correlated with high tumor stage CRC and poor prognosis and survival in a large cohort of CRC patients, being also associated to high expression of nuclear YAP1. All these data point at DUSP10 as a downstream protein in COX-2 signaling and provide evidence of the role of DUSP10 in CRC progression via YAP1 regulation (Jimenez-Martinez et al, 2019a). Interestingly, an inhibitor of DUSP10 have been described (Hommo et al, 2015), supporting its use in CRC.…”

Section: Dual-specificity Mapk Phosphatase 10mentioning

confidence: 73%

“…This dephosphorylation retains YAP in the nucleus. In fact, we found that high amounts of DUSP10 and YAP1 are located in the nucleus of CRC cells (Jimenez-Martinez et al, 2019a). Additionally, the quantity of nuclear DUSP10 in CRC tumor biopsies is directly correlated with high tumor stage CRC and poor prognosis and survival in a large cohort of CRC patients, being also associated to high expression of nuclear YAP1.…”

Section: Dual-specificity Mapk Phosphatase 10mentioning

confidence: 74%

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Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer

et al. 2020

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Colorectal cancer (CRC) is one of the most common and recurrent types of cancer, with high mortality rates. Several clinical trials and meta-analyses have determined that the use of pharmacological inhibitors of cyclooxygenase 2 (COX-2), the enzyme that catalyses the rate-limiting step in the synthesis of prostaglandins (PG) from arachidonic acid, can reduce the incidence of CRC as well as the risk of recurrence of this disease, when used together with commonly used chemotherapeutic agents. These observations suggest that inhibition of COX-2 may be useful in the treatment of CRC, although the current drugs targeting COX-2 are not widely used since they increase the risk of health complications. To overcome this difficulty, a possibility is to identify genes regulated by COX-2 activity that could give an advantage to the cells to form tumors and/or metastasize. The modulation of those genes as effectors of COX-2 may cancel the beneficial effects of COX-2 in tumor transformation and metastasis. A review of the available databases and literature and our own data have identified some interesting molecules induced by prostaglandins or COX-2 that have been also described to play a role in colon cancer, being thus potential pharmacological targets in colon cancer. Among those mPGES-1, DUSP4, and 10, Programmed cell death 4, Trop2, and many from the TGFb and p53 pathways have been identified as genes upregulated in response to COX-2 overexpression or PGs in colon carcinoma lines and overexpressed in colon tumor tissue. Here, we review the available evidence of the potential roles of those molecules in colon cancer in the context of PG/ COX signaling pathways that could be critical mediators of some of the tumor growth and metastasis advantage induced by COX-2. At the end, this may allow defining new therapeutic targets/drugs against CRC that could act specifically against tumor cells and would be effective in the prevention and treatment of CRC, lacking the unwanted side effects of COX-2 pharmacological inhibitors, providing alternative approaches in colon cancer.

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Section: Cox-2 and The Tgf-b Pathwaysupporting

confidence: 59%

Section: Dual-specificity Mapk Phosphatase 10mentioning

confidence: 73%

Section: Dual-specificity Mapk Phosphatase 10mentioning

confidence: 74%

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Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer

et al. 2020

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“…We sought to investigate the mRNA levels of Ptgs2 in our mouse model of colon cancer, CT26 cells-Balb/c mice, as well as those of the group of COX2 effector genes we identified in human colon cancer. First, we confirmed that COX2 activity can change the expression of some of the genes we have identified as COX2-target or effector genes in human cancer (Stamatakis et al, 2015;Jiménez-Martínez et al, 2019;Jiménez-Segovia et al, 2019;Hidalgo-Estévez et al, 2020), namely, Ptge2, Ptges, Dusp10, Pmepa1, Inhba, Il15, and Nfkbia. There was also a tendency for Klf4, Tacstd2, Nfat5, Tgfb1, and Il15ra to be upregulated with COX2 overexpression in CT26 cells, as it happened in HT29 human cells, but without reaching statistical significance.…”

Section: Discussionsupporting

confidence: 68%

Cyclooxygenase 2 Effector Genes as Potential Inflammation-Related Biomarkers for Colorectal Cancer Circulating Tumor Cells Detection by Liquid Biopsy

et al. 2022

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Cyclooxygenase 2 (COX2) has been implicated in cancer development and metastasis. We have identified several COX2-regulated inflammation-related genes in human colorectal cancer cells and shown that some of them play important roles in tumor progression. In this work, we have studied the COX2-regulated genes in the mouse colorectal cancer cell line CT26, to find that many are also regulated by COX2 over-expression. On the other hand, we generated a CT26 cell line expressing Gfp and Luciferase, to study tumor growth and metastasis in immunocompetent Balb/c mice. We then collected solid tissue, and blood samples, from healthy and tumor-bearing mice. Using the Parsortix® cell separation system and taking advantage of the fact that the tumor cells expressed Gfp, we were able to identify circulating tumor cells (CTCs) in some of the mice. We compared the mRNA expression levels of Ptgs2 and effector genes in the samples obtained from tumor-bearing or healthy mice, namely, tumor or healthy colon, Ficoll purified buffy coat, and Parsortix-isolated cells to find different patterns between healthy, tumor-bearing mice with or without CTCs. Although for genes like Il15 we did not observe any difference between healthy and tumor-bearing mice in Ficoll or Parsortix samples; others, such as Egr1, Zc3h12a, Klf4, or Nfat5, allowed distinguishing for cancer or CTC presence. Gene expression analysis in Ficoll or Parsortix processed samples, after liquid biopsy, may offer valuable diagnostic and prognostic information and thus should be further studied.

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“…By acting as a transcriptional coactivator, YAP1 can induce the expression of MALAT1 and also stabilize TF HIF1α [ 83 , 84 ]. Furthermore, YAP1 can interact with dual-specificity phosphatase 10 (DUSP10/MKP5) [ 85 ]. Dual-specificity phosphatases are well known to be negative regulators of YAP1 on p38 and MAPK pathways [ 86 ].…”

Section: Resultsmentioning

confidence: 99%

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications

Ting

Chen

2022

IJMS

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The coronavirus disease 2019 (COVID-19) epidemic is currently raging around the world at a rapid speed. Among COVID-19 patients, SARS-CoV-2-associated acute respiratory distress syndrome (ARDS) is the main contribution to the high ratio of morbidity and mortality. However, clinical manifestations between SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS are quite common, and their therapeutic treatments are limited because the intricated pathophysiology having been not fully understood. In this study, to investigate the pathogenic mechanism of SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS, first, we constructed a candidate host-pathogen interspecies genome-wide genetic and epigenetic network (HPI-GWGEN) via database mining. With the help of host-pathogen RNA sequencing (RNA-Seq) data, real HPI-GWGEN of COVID-19-associated ARDS and non-viral ARDS were obtained by system modeling, system identification, and Akaike information criterion (AIC) model order selection method to delete the false positives in candidate HPI-GWGEN. For the convenience of mitigation, the principal network projection (PNP) approach is utilized to extract core HPI-GWGEN, and then the corresponding core signaling pathways of COVID-19-associated ARDS and non-viral ARDS are annotated via their core HPI-GWGEN by KEGG pathways. In order to design multiple-molecule drugs of COVID-19-associated ARDS and non-viral ARDS, we identified essential biomarkers as drug targets of pathogenesis by comparing the core signal pathways between COVID-19-associated ARDS and non-viral ARDS. The deep neural network of the drug–target interaction (DNN-DTI) model could be trained by drug–target interaction databases in advance to predict candidate drugs for the identified biomarkers. We further narrowed down these predicted drug candidates to repurpose potential multiple-molecule drugs by the filters of drug design specifications, including regulation ability, sensitivity, excretion, toxicity, and drug-likeness. Taken together, we not only enlighten the etiologic mechanisms under COVID-19-associated ARDS and non-viral ARDS but also provide novel therapeutic options for COVID-19-associated ARDS and non-viral ARDS.

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DUSP10 Is a Regulator of YAP1 Activity Promoting Cell Proliferation and Colorectal Cancer Progression

Cited by 10 publications

References 40 publications

Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer

Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer

Cyclooxygenase 2 Effector Genes as Potential Inflammation-Related Biomarkers for Colorectal Cancer Circulating Tumor Cells Detection by Liquid Biopsy

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications

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