scholarly journals Follistatin-Like 3 Enhances Invasion and Metastasis via β-Catenin-Mediated EMT and Aerobic Glycolysis in Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuqiang Li ◽  
Mengxiang Tian ◽  
Wenxue Liu ◽  
Dan Wang ◽  
Zhongyi Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Tumor Stage ◽  
Invasion And Metastasis ◽  
Poor Prognostic Factor ◽  
Node Metastasis ◽  
Pathway Activation ◽  
Promising Therapeutic Target ◽  
Metastatic Capacity

Previous studies reported that Follistatin-like 3 (FSTL3) is abundantly expressed in several solid tumors and participate in the regulation of cell metabolism. However, the clinico-pathological significance, biological role and molecular mechanism of FSTL3 in colorectal cancer (CRC) is still unclear. Here we report that the expression level of FSTL3 in colon cancer specimens was significantly higher, compared to normal tissue and interestingly, the expression of FSTL3 was related to lymph node metastasis, tumor stage, tumor size, and intravascular emboli (IVE). As an upstream molecular event, we found that transcriptional regulation of FSTL3 was highly dependent on YAP1 de-phosphorylation events and that increased FSTL3 expression readily activated the β-Catenin pathway, which is a well-known signaling hub that promotes EMT processes and aerobic glycolysis in cancer cells. We found that elevated FSTL3 expression strongly promotes migration, invasion and metastatic formation of CRC cells by directly activating β-Catenin -mediated EMT and aerobic glycolysis. In the xenograft mouse model, FSTL3 expression was linked to increased metastatic formation of CRC cells. Together, the activation of YAP1 induces FSTL3 expression. FSTL3-mediated β-Catenin pathway activation promotes EMT and aerobic glycolysis and therefore affecting the invasive and metastatic capacity of CRC cells. The abundant FSTL3 expression is a poor prognostic factor and pharmacological targeting of YAP1 can counteract FSTL3 expression, suggesting a promising therapeutic target for anti-metastatic strategies in patients suffering from CRC.

scholarly journals Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer

2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Tumor Stage ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Node Metastasis

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

scholarly journals Identification of circular RNA hsa_circ_0044556 and its effect on the development and progression of colorectal cancer

2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Tumor Stage ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Node Metastasis

Abstract Background Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNAs in the development and progression of colorectal cancer (CRC) remains unclear. Methods First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines. Results hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression. Conclusion hsa_circ_0044556 promoted the development and progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

scholarly journals High Expression of Both Resistin and Fascin-1 Predicts a Poor Prognosis in Patients with Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Chao-Qun Wang ◽  
Yan Wang ◽  
Bi-Fei Huang ◽  
Chih-Hsin Tang ◽  
Zhang Du ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Tumor Invasion ◽  
Poor Prognosis ◽  
Prognostic Significance ◽  
Tumor Stage ◽  
Potential Therapeutic Target ◽  
Node Metastasis ◽  
High Level

Emerging evidence indicates that resistin and fascin-1 may possess a causal role in the development of several types of cancers. However, the clinical significance of resistin expression in colorectal cancer (CRC) tissues is unclear, and there are no reports of any correlation between resistin and fascin-1. Our analyses explored the expression of resistin in CRC tissue and analyzed the clinical and prognostic significance of the observed positive correlation between resistin and fascin-1. The rate of strongly positive resistin expression (27.5%) was significantly higher in CRC tissues than in normal colorectal tissues (5.2%). Strongly positive resistin expression is related to multiple poor prognostic factors in CRC, including depth of tumor invasion, lymph node metastasis, and tumor stage. In this study, survival was worse in CRC patients with high levels of both resistin and fascin-1 expression than in those with high levels of only one protein or normal levels of both proteins. We suggest that a combined high level of resistin and fascin-1 expression correlates reliably with survival in CRC, so it may serve as a potential therapeutic target.

scholarly journals Rab1A promotes cell proliferation and migration by upregulating Gli1 in colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chaozhong Peng ◽  
Xiao Li ◽  
Zhixue Ye ◽  
Wenqing Wu
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Node Metastasis ◽  
Cell Proliferation And Migration ◽  
Promising Therapeutic Target ◽  
Promotive Effect ◽  
Guanosine Triphosphatase ◽  
And Migration ◽  
Proliferation And Migration

AbstractRab1A, as a highly conserved small guanosine triphosphatase (GTPase), plays contentious roles in different types of cancers. The role of Rab1A in colorectal cancer (CRC) has been described in previous studies, but the molecular mechanisms of Rab1A in CRC remain far from being addressed. In the present study, we found that Rab1A expression was significantly upregulated in CRC tissues and increased Rab1A expression correlated with tumor size, lymph node metastasis (LNM) and tumor-node-metastasis (TNM) stage of CRC patients. We also found that Rab1A exerts its promotive effect on CRC cell proliferation, migration and EMT progress. Further mechanistic experiments showed that glioma-associated oncogene-1 (Gli1), as a key transcriptional factor of the Hedgehog pathway, was implicated in Rab1A-mediated regulation of CRC cell proliferation and migration. In addition, Rab1A upregulated Gli1 expression through Smoothened homolog (SMO)-independent pathway. Finally, Rab1A activated mechanistic target of rapamycin (mTOR) signaling in CRC cells. Collectively, our results define Rab1A as a novel regulator of Gli1 to promote CRC cell proliferation and migration, and suggest that the Rab1A/mTOR/Gli1 axis may serve as a promising therapeutic target for the treatment of CRC.

scholarly journals Insights into the Role of microRNAs in Colorectal Cancer (CRC) Metabolism

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2462 ◽  
Author(s):  
Kha Wai Hon ◽  
Syafiq Asnawi Zainal Abidin ◽  
Iekhsan Othman ◽  
Rakesh Naidu
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Regulation Of Gene Expression ◽  
High Energy ◽  
Metabolic Reprogramming ◽  
Cancer Hallmarks ◽  
Fatty Acids Metabolism

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers, with a high mortality rate globally. The pathophysiology of CRC is mainly initiated by alteration in gene expression, leading to dysregulation in multiple signalling pathways and cellular processes. Metabolic reprogramming is one of the important cancer hallmarks in CRC, which involves the adaptive changes in tumour cell metabolism to sustain the high energy requirements for rapid cell proliferation. There are several mechanisms in the metabolic reprogramming of cancer cells, such as aerobic glycolysis, oxidative phosphorylation, lactate and fatty acids metabolism. MicroRNAs (miRNAs) are a class of non-coding RNAs that are responsible for post-transcriptional regulation of gene expression. Differential expression of miRNAs has been shown to play an important role in different aspects of tumorigenesis, such as proliferation, apoptosis, and drug resistance, as well as metabolic reprogramming. Increasing evidence also reports that miRNAs could function as potential regulators of metabolic reprogramming in CRC cells. This review provides an insight into the role of different miRNAs in regulating the metabolism of CRC cells as well as to discuss the potential role of miRNAs as biomarkers or therapeutic targets in CRC tumour metabolism.

scholarly journals The prognostic role of c-MYC amplification in schistosomiasis-associated colorectal cancer

2020 ◽  
Vol 50 (4) ◽  
pp. 446-455 ◽  
Author(s):  
Weiyu Pan ◽  
Weixia Wang ◽  
Jie Huang ◽  
Kui Lu ◽  
Sinian Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Positive Lymph Node ◽  
Prognostic Role ◽  
Full Cohort ◽  
Poor Prognostic Factor ◽  
Node Metastasis ◽  
Significant Difference

Abstract Objective The purpose of this study was to explore the prognostic role of c-MYC amplification in colorectal cancer, particularly in schistosomiasis-associated colorectal cancer. Methods Three hundred and fifty four cases of colorectal cancer, which were from Qingpu Branch of Zhongshan Hospital affiliated to Fudan University, were retrospectively analyzed in a tissue microarray (TMA) format, with fluorescence in situ hybridization (FISH) assay and immunohistochemistry (IHC). Results c-MYC gene amplification was found in 14.1% (50 out of 354) of patients with colorectal cancer and was correlated with old age (P = 0.028), positive lymph node metastasis (P = 0.004) and advanced stage tumors (P = 0.002). The overexpression of c-MYC was closely associated with the amplification status (P = 0.023). Kaplan–Meier survival curves for overall survival (OS) showed a statistically significant difference for patients with c-MYC amplification in full cohort of colorectal cancer, stage III-IV set and patients with lymph node metastasis (P = 0.002, 0.034, 0.012, respectively). Further analysis found c-MYC amplification associated with poorer survival in the subgroup of colorectal cancer with schistosomiasis (CRC-S, P < 0.001), but not in colorectal cancer without schistosomiasis (CRC-NS, P = 0.155). By multivariate analysis, c-MYC amplification was an independent poor-prognostic factor in CRC-S set (P = 0.046). Conclusions Our study firstly found c-MYC amplification could predict poor prognosis in schistosomiasis-associated colorectal cancer, but not in colorectal cancer without schistosomiasis.

PLOD2 promotes aerobic glycolysis and cell progression in colorectal cancer by upregulating HK2

2020 ◽  
Vol 98 (3) ◽  
pp. 386-395 ◽  
Author(s):  
Wenwu Du ◽  
Ning Liu ◽  
Yafeng Zhang ◽  
Xi Liu ◽  
Yuanhong Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Aerobic Glycolysis ◽  
Tumor Grade ◽  
Protein Levels ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Promising Therapeutic Target ◽  
Cell Progression ◽  
N Stage

The purpose of this study was to characterize the expression of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a membrane-bound homodimeric enzyme that specifically hydroxylates lysine in the telopeptide of procollagens, and assess the clinical significance of PLOD2 in colorectal cancer (CRC). Our results show that PLOD2 is highly expressed in CRC tumor tissues and cell lines, both at the mRNA and protein levels. Next, we found that PLOD2 was positively correlated with tumor grade (P = 0.001), T stage (P = 0.001), N stage (P < 0.001), and an advanced TNM stage (P < 0.001). Knockdown of PLOD2 attenuated CRC cell proliferation, migration, and invasiveness, in vitro. Our analysis of the mechanism behind the effects of PLOD2 suggests that PLOD2 affected glycolysis by regulating the expression of hexokinase 2 (HK2). HK2 reverses the inhibitory effects of PLOD2 knockdown in CRC. Furthermore, the data suggest that PLOD2 regulates the expression of HK2 via the STAT3 signaling pathway. Survival analysis revealed that high expression levels of PLOD2 (HR = 3.800, P < 0.001) and HK2 expression (HR = 10.222, P < 0.001) correlated with the overall survival rate. After analyzing their expression and correlation, PLOD2 positively correlated with HK2 (r = 0.590, P < 0.001). Our findings have revealed that PLOD2 is a novel regulatory factor in glucose metabolism, exerted via controlling HK2 expression in CRC cells, suggesting PLOD2 as a promising therapeutic target for CRC treatment.

scholarly journals Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer

2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Tumor Stage ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Node Metastasis

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

Sign in / Sign up

Export Citation Format

Share Document