The critical role of dysregulated FOXM1–PLAUR signaling in human colon cancer progression and metastasis.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 405-405
Author(s):  
Dawei Li ◽  
Ping Wei ◽  
Zhihai Peng ◽  
Chen Huang ◽  
Huamei Tang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Critical Role ◽  
Cox Proportional Hazards Model ◽  
Urokinase Plasminogen Activator Receptor ◽  
Altered Expression ◽  
Colon Cancer Progression ◽  
Foxm1 Expression ◽  
The Impact

405 Background: The mammalian Forkhead Box (Fox) transcription factor FOXM1 is implicated in tumorigenesis including mouse intestinal cancer. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. Methods: We investigated FOXM1 expression in 203 cases of primary colon cancer and matched normal colon tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on colon cancer growth and metastasis using in vitro and animal models of colon cancer. Results: We found weak expression of FOXM1 protein in the colon mucosa, whereas we observed strong FOXM1 expression in tumor-cell nuclei of colon cancer and lymph node metastases. A Cox proportional hazards model revealed that FOXM1 expression was an independent prognostic factor in multivariate analysis. Experimentally, overexpression of FOXM1 by gene transfer significantly promoted the growth and metastasis of colon cancer cells in orthotopic mouse models, whereas knockdown of FOXM1 expression by small interfering RNA did the opposite. Promotion of colon tumorigenesis by FOXM1 directly and significantly correlated with activation of urokinase plasminogen activator receptor (PLAUR) expression and elevation of invasion and metastasis. Conclusions: Given the importance of FOXM1 in regulation of the expression of genes key to cancer biology, dysregulated expression and activation of FOXM1 may play important roles in colon cancer progression and metastasis.

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.

scholarly journals S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

2020 ◽  
Author(s):  
Guiyang Wu ◽  
Chongshan Wu ◽  
Fubo Ye ◽  
Xiongwen Zhu ◽  
Zaiping Chen
Keyword(s):  
Cancer Cell ◽  
Proportional Hazards Model ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Altered Expression ◽  
S100a4 Expression ◽  
The Impact

Abstract Background Glucose metabolism transformation plays critical role in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. S100A4 has been identified as an oncogene in a variety of cancers. However, its role in the cancer cell glucose reprogramming has been seldom reported. The aim of this study was to examine the role of S100A4 in aerobic glycolysis in colorectal cancer (CRC). Methods We investigated S100A4 expression in 224 cases of primary CRC and matched normal colonic tissue specimens, and explored the underlying mechanisms of altered S100A4 expression as well as the impact of this altered expression on CRC growth and glycolysis using in vitro and animal models of CRC. Results S100A4 was more highly expressed in CRC tissues than in the adjacent normal tissues (59.4% vs 17.4%, P <0.05). Higher S100A4 expression was associated with advanced node stage ( P =0.018) and larger tumor size ( P =0.035). A Cox proportional hazards model suggested that S100A4 expression was an independent prognostic factor for both OS (HR: 3.967, 95%CI: 1.919-8.200, P <0.001) and DFS (HR: 4.350, 95%CI: 2.264-8.358, P <0.001) in CRC after surgery. Experimentally, silencing S100A4 expression significantly decreased the growth and glycolysis rate of CRC both in vitro and in vivo . Mechanically, S100A4 could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element–luciferase activity in CRC cells. Conclusions These results disclose a novel role for S100A4 in reprogramming the metabolic process in CRC by affecting the HIF-1α activity and provide potential prognostic predictors for CRC.

scholarly journals S100A4 promotes colorectal carcinoma growth by enhancing aerobic glycolysis

2020 ◽  
Author(s):  
Guiyang Wu ◽  
Chongshan Wu ◽  
Fubo Ye ◽  
Xiongwen Zhu ◽  
Zaiping Chen
Keyword(s):  
Cancer Cell ◽  
Proportional Hazards Model ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Altered Expression ◽  
S100a4 Expression ◽  
The Impact

Abstract Background Glucose metabolism transformation plays critical role in cancer cell malignancies maintenance. Aberrant cancer cell metabolism is considered to be the hallmark of cancer. S100A4 has been identified as an oncogene in a variety of cancers. However, its role in the cancer cell glucose reprogramming has been seldom reported. The aim of this study was to examine the role of S100A4 in aerobic glycolysis in colorectal cancer (CRC). Methods We investigated S100A4 expression in 224 cases of primary CRC and matched normal colonic tissue specimens, and explored the underlying mechanisms of altered S100A4 expression as well as the impact of this altered expression on CRC growth and glycolysis using in vitro and animal models of CRC. Results S100A4 was more highly expressed in CRC tissues than in the adjacent normal tissues (59.4% vs 17.4%, P <0.05). Higher S100A4 expression was associated with advanced node stage ( P =0.018) and larger tumor size ( P =0.035). A Cox proportional hazards model suggested that S100A4 expression was an independent prognostic factor for both OS (HR: 3.967, 95%CI: 1.919-8.200, P <0.001) and DFS (HR: 4.350, 95%CI: 2.264-8.358, P <0.001) in CRC after surgery. Experimentally, silencing S100A4 expression significantly decreased the growth and glycolysis rate of CRC both in vitro and in vivo . Mechanically, S100A4 could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element–luciferase activity in CRC cells. Conclusions These results disclose a novel role for S100A4 in reprogramming the metabolic process in CRC by affecting the HIF-1α activity and provide potential prognostic predictors for CRC.

scholarly journals The Critical Role of Dysregulated FOXM1–PLAUR Signaling in Human Colon Cancer Progression and Metastasis

2012 ◽  
Vol 19 (1) ◽  
pp. 62-72 ◽  
Author(s):  
Dawei Li ◽  
Ping Wei ◽  
Zhihai Peng ◽  
Chen Huang ◽  
Huamei Tang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Critical Role ◽  
Human Colon ◽  
Human Colon Cancer ◽  
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 A non-toxic, reversibly released imaging probe for oral cancer that is derived from natural compounds

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Magda Ghanim ◽  
Nicola Relitti ◽  
Gavin McManus ◽  
Stefania Butini ◽  
Andrea Cappelli ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Progression ◽  
Intraoperative Imaging ◽  
Critical Role ◽  
Water Soluble ◽  
Stem Cell Marker ◽  
Squamous Cells ◽  
Tissue Identification ◽  
Tumorigenic Potential ◽  
The Impact

AbstractCD44 is emerging as an important receptor biomarker for various cancers. Amongst these is oral cancer, where surgical resection remains an essential mode of treatment. Unfortunately, surgery is frequently associated with permanent disfigurement, malnutrition, and functional comorbidities due to the difficultly of tumour removal. Optical imaging agents that can guide tumour tissue identification represent an attractive approach to minimising the impact of surgery. Here, we report the synthesis of a water-soluble fluorescent probe, namely HA-FA-HEG-OE (compound 1), that comprises components originating from natural sources: oleic acid, ferulic acid and hyaluronic acid. Compound 1 was found to be non-toxic, displayed aggregation induced emission and accumulated intracellularly in vesicles in SCC-9 oral squamous cells. The uptake of 1 was fully reversible over time. Internalization of compound 1 occurs through receptor mediated endocytosis; uniquely mediated through the CD44 receptor. Uptake is related to tumorigenic potential, with non-tumorigenic, dysplastic DOK cells and poorly tumorigenic MCF-7 cells showing only low intracellular levels and highlighting the critical role of endocytosis in cancer progression and metastasis. Together, the recognised importance of CD44 as a cancer stem cell marker in oral cancer, and the reversible, non-toxic nature of 1, makes it a promising agent for real time intraoperative imaging.

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 Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Jiao Wu ◽  
Sai-Ching Jim Yeung ◽  
Sicheng Liu ◽  
Aiham Qdaisat ◽  
Dewei Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Weight Loss ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Colorectal Cancer Patient ◽  
Nutrition Support ◽  
Immunodeficient Mice ◽  
The Impact

AbstractWeight loss and cachexia are common problems in colorectal cancer patients; thus, parenteral and enteral nutrition support play important roles in cancer care. However, the impact of nonessential amino acid components of nutritional intake on cancer progression has not been fully studied. In this study, we discovered that gastrointestinal cancer patients who received cysteine as part of the parenteral nutrition had shorter overall survival (P < 0.001) than those who did not. Cystine indeed robustly promotes colon cancer cell growth in vitro and in immunodeficient mice, predominately by inhibiting SESN2 transcription via the GCN2-ATF4 axis, resulting in mTORC1 activation. mTORC1 inhibitors Rapamycin and Everolimus block cystine-induced cancer cell proliferation. In addition, cystine confers resistance to oxaliplatin and irinotecan chemotherapy by quenching chemotherapy-induced reactive oxygen species via synthesizing glutathione. We demonstrated that dietary deprivation of cystine suppressed colon cancer xenograft growth without weight loss in mice and boosted the antitumor effect of oxaliplatin. These findings indicate that cyst(e)ine, as part of supplemental nutrition, plays an important role in colorectal cancer and manipulation of cyst(e)ine content in nutritional formulations may optimize colorectal cancer patient survival.

Sign in / Sign up

Export Citation Format

Share Document