scholarly journals Loss of TGFβ signaling promotes colon cancer progression and tumor-associated inflammation

Oncotarget ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 3826-3839 ◽  
Author(s):  
Daniel R. Principe ◽  
Brian DeCant ◽  
Jonas Staudacher ◽  
Dominic Vitello ◽  
Riley J. Mangan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Tgfβ Signaling ◽  
Colon Cancer Progression

scholarly journals Interplay between transforming growth factor-β and Nur77 in dual regulations of inhibitor of differentiation 1 for colonic tumorigenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Boning Niu ◽  
Jie Liu ◽  
Ben Lv ◽  
Jiacheng Lin ◽  
Xin Li ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Growth Factor ◽  
Mrna Expression ◽  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tgfβ Signaling ◽  
Colon Cancers ◽  
Colon Cancer Progression ◽  
Inhibitor Of Differentiation 1

AbstractThe paradoxical roles of transforming growth factor-β (TGFβ) signaling and nuclear receptor Nur77 in colon cancer development are known but the underlying mechanisms remain obscure. Inhibitor of differentiation 1 (ID1) is a target gene of TGFβ and a key promoter for colon cancer progression. Here, we show that Nur77 enhances TGFβ/Smad3-induced ID1 mRNA expression through hindering Smurf2-mediated Smad3 mono-ubiquitylation, resulting in ID1 upregulation. In the absence of TGFβ, however, Nur77 destabilizes ID1 protein by promoting Smurf2-mediated ID1 poly-ubiquitylation, resulting in ID1 downregulation. Interestingly, TGFβ stabilizes ID1 protein by switching Nur77 interaction partners to inhibit ID1 ubiquitylation. This also endows TGFβ with an active pro-tumorigenic action in Smad4-deficient colon cancers. Thus, TGFβ converts Nur77’s role from destabilizing ID1 protein and cancer inhibition to inducing ID1 mRNA expression and cancer promotion, which is highly relevant to colon cancer stemness, metastasis and oxaliplatin resistance. Our data therefore define the integrated duality of Nur77 and TGFβ signaling in regulating ID1 expression and provide mechanistic insights into the paradoxical roles of TGFβ and Nur77 in colon cancer progression.

Role of MicroRNAs in Colon Cancer Progression and Metastasis

2020 ◽  
Vol 20 ◽  
Author(s):  
Shruthi Sanjitha Sampath ◽  
Sivaramakrishnan Venkatabalsubramanian ◽  
Satish Ramalingam
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Tumour Progression ◽  
Intestinal Barrier ◽  
Colon Cancer Progression ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic Strategies

: MicroRNAs regulate gene expression at the posttranscriptional level by binding to the mRNA of their target genes. The dysfunction of miRNAs is strongly associated with the inflammation of the colon. Besides, some microRNAs are shown to suppress tumours while others promote tumour progression and metastasis. Inflammatory bowel diseases include Crohn’s disease and Ulcerative colitis which increase the risk factor for inflammation-associated colon cancer. MicroRNAs are shown to be involved in gastrointestinal pathologies, by targeting the transcripts encoding proteins of the intestinal barrier and their regulators that are associated with inflammation and colon cancer. Detection of these microRNAs in the blood, serum, tissues, faecal matter, etc will enable us to use these microRNAs as biomarkers for early detection of the associated malignancies and design novel therapeutic strategies to overcome the same. Information on MicroRNAs can be applied for the development of targeted therapies against inflammation-mediated colon cancer.

Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression

MicroRNA ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 68-75 ◽  
Author(s):  
Jeyalakshmi Kandhavelu ◽  
Kumar Subramanian ◽  
Amber Khan ◽  
Aadilah Omar ◽  
Paul Ruff ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Target Prediction ◽  
Computational Prediction ◽  
Initial Step ◽  
Kegg Pathways ◽  
Candidate Mirnas ◽  
Common Cancer ◽  
Colon Cancer Progression

Background:Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs. </P><P> Methods: The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis.Results:We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated.These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.

scholarly journals Proteins are potent biomarkers to detect colon cancer progression

2017 ◽  
Vol 24 (6) ◽  
pp. 1212-1221 ◽  
Author(s):  
Palaniselvam Kuppusamy ◽  
Natanamurugaraj Govindan ◽  
Mashitah M. Yusoff ◽  
Solachuddin J.A. Ichwan
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Colon Cancer Progression

The upregulation of PYCR2 is associated with aggressive colon cancer progression and a poor prognosis

2021 ◽  
Vol 572 ◽  
pp. 20-26
Author(s):  
Sitong Wang ◽  
Linaer Gu ◽  
Lili Huang ◽  
Juemin Fang ◽  
Zhuqing Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Colon Cancer Progression

scholarly journals Phosphatase and Tensin Homolog (PTEN) Represses Colon Cancer Progression through Inhibiting Paxillin Transcription via PI3K/AKT/NF-κB Pathway

2015 ◽  
Vol 290 (24) ◽  
pp. 15018-15029 ◽  
Author(s):  
Ling-Li Zhang ◽  
Gang-Gang Mu ◽  
Qian-Shan Ding ◽  
Yan-Xia Li ◽  
Yun-bo Shi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Colon Cancer Progression

The extracellular matrix protein mindin attenuates colon cancer progression by blocking angiogenesis via Egr-1-mediated regulation

Oncogene ◽  
2017 ◽  
Vol 37 (5) ◽  
pp. 601-615 ◽  
Author(s):  
L-F Wang ◽  
Y-S Liu ◽  
B Yang ◽  
P Li ◽  
X-S Cheng ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Extracellular Matrix ◽  
Cancer Progression ◽  
Matrix Protein ◽  
Extracellular Matrix Protein ◽  
Colon Cancer Progression

Long non-coding RNA XIST sponges miR-34a to promotes colon cancer progression via Wnt/β-catenin signaling pathway

Gene ◽  
2018 ◽  
Vol 665 ◽  
pp. 141-148 ◽  
Author(s):  
Ningning Sun ◽  
Guozun Zhang ◽  
Yingying Liu
Keyword(s):  
Colon Cancer ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Non Coding Rna ◽  
Colon Cancer Progression ◽  
Long Non Coding Rna

scholarly journals Increased nicotinamide adenine dinucleotide pool promotes colon cancer progression by suppressing reactive oxygen species level

2018 ◽  
Vol 110 (2) ◽  
pp. 629-638 ◽  
Author(s):  
Sun M. Hong ◽  
Sung W. Hwang ◽  
Taejun Wang ◽  
Chang W. Park ◽  
Yeon‐Mi Ryu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Colon Cancer ◽  
Cancer Progression ◽  
Nicotinamide Adenine Dinucleotide ◽  
Reactive Oxygen ◽  
Species Level ◽  
Reactive Oxygen Species Level ◽  
Nicotinamide Adenine ◽  
Oxygen Species ◽  
Colon Cancer Progression

scholarly journals The Role of M3 Muscarinic Receptor Ligand-Induced Kinase Signaling in Colon Cancer Progression

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 308 ◽  
Author(s):  
Mazen Tolaymat ◽  
Shannon Larabee ◽  
Shien Hu ◽  
Guofeng Xie ◽  
Jean-Pierre Raufman
Keyword(s):  
Colon Cancer ◽  
Protein Kinase ◽  
Muscarinic Receptor ◽  
Cancer Progression ◽  
The United States ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Colon Cancer Progression ◽  
M3 Muscarinic Receptor ◽  
The Impact

Despite a reduction in incidence over the past decade, colon cancer remains the second most common cause of cancer death in the United States; recent demographics suggest this disease is now afflicting younger persons. M3 muscarinic receptor (M3R) mRNA and protein are over-expressed in colon cancer, and M3R can be activated by both traditional (e.g., acetylcholine) and non-traditional (e.g., bile acids) muscarinic ligands. In this review, we weigh the data supporting a prominent role for key protein kinases downstream of M3R activation in promoting colon cancer progression and dissemination. Specifically, we explore the roles that downstream activation of the mitogen activated protein kinase/extracellular signal-related kinase (MAPK/ERK), protein kinase C, p38 MAPK, and phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathways play in mediating colon cancer cell proliferation, survival, migration and invasion. We assess the impact of M3R-stimulated induction of selected matrix metalloproteinases germane to these hallmarks of colon cancer progression. In this context, we also critically review the reproducibility of findings derived from a variety of in vivo and in vitro colon cancer models, and their fidelity to human disease. Finally, we summarize the therapeutic potential of targeting various steps from ligand-M3R interaction to the activation of key downstream molecules.

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