The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression

Weili, Gao; Ye, Guo‐Chao; Liu, Liwei; Lu, Wei

doi:10.3892/ol.2018.8305

Cited by 11 publications

(12 citation statements)

References 36 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This in turn promoted the invasion and metastatic spread of tumor cells [101]. A downregulation of Rap1GAP in colorectal cancer patients was associated with increased MMP9 expression and poorer survival rates [56,102]. This result is in line with a study on gastric cancer, indicating that downregulation of Rap1GAP in patients significantly correlated with an upregulation of MMP9 with a poor prognosis [103].…”

Section: Rap1 Signaling Regulates Matrix Metalloproteinases (Mmps)-desupporting

confidence: 75%

“…Rap1 has been reported to serve an important role in regulating cadherin expression ( Figure 5). The downregulation of Rap1GAP was frequently associated in tumor cell lines which underwent epithelial-to-mesenchymal transition (EMT) [46,56]. A common feature of EMT is the reduction of E-cadherin expression, resulting in the loss of epithelial cell-cell adhesive junctions and contact inhibition of proliferation [90][91][92].…”

Section: Rap1 Promotes Emt Via Downregulation Of E-cadherin Expressionmentioning

confidence: 99%

“…A common feature of EMT is the reduction of E-cadherin expression, resulting in the loss of epithelial cell-cell adhesive junctions and contact inhibition of proliferation [90][91][92]. Recent study showed that upregulation of Rap1GAP was positively associated with the expression of E-cadherin in gastric cancer and colorectal cancer [46,56]. Mechanistic study showed that Rap1A enhanced the expression of EMT markers via activation of ERK, MAPK, and Notch signaling pathway [93].…”

Section: Rap1 Promotes Emt Via Downregulation Of E-cadherin Expressionmentioning

confidence: 99%

“…These findings suggest the potential role of Rap1GAP as a tumor suppressor. In colorectal, gastric and endometrial cancers, clinical studies have demonstrated that the loss of Rap1GAP expression was correlated with negative clinicopathological outcomes, such as invasion depth, lymph node metastasis, advanced TNM stages and poor overall survival (OS) as determined by Kaplan-Meier survival analyses [46,56]. Hence, these results clearly indicated that Rap1GAP may be used to target and identify patients who have a higher risk of recurrence and mortality, and personalized treatment can be given to improve patients' clinical outcomes.…”

Section: Therapeutic Potential Of Rap1 Signaling In Cancersmentioning

confidence: 99%

See 3 more Smart Citations

The Role of Ras-Associated Protein 1 (Rap1) in Cancer: Bad Actor or Good Player?

et al. 2020

View full text Add to dashboard Cite

Metastasis is known as the most life-threatening event in cancer patients. In principle, the immune system can prevent tumor development. However, dysfunctional T cells may fail to eliminate the tumor cells effectively and provide additional survival advantages for tumor proliferation and metastasis. Constitutive activation of Ras-associated protein1 (Rap1) has not only led to T cell anergy, but also inhibited autophagy and supported cancer progression through various oncogenic events. Inhibition of Rap1 activity with its negative regulator, Rap1GAP, impairs tumor progression. However, active Rap1 reduces tumor invasion in some cancers, indicating that the pleiotropic effects of Rap1 signaling in cancers could be cancer-specific. All in all, targeting Rap1 signaling and its regulators could potentially control carcinogenesis, metastasis, chemoresistance and immune evasion. Rap1GAP could be a promising therapeutic target in combating cancer.

show abstract

Section: Rap1 Signaling Regulates Matrix Metalloproteinases (Mmps)-desupporting

confidence: 75%

Section: Rap1 Promotes Emt Via Downregulation Of E-cadherin Expressionmentioning

confidence: 99%

Section: Rap1 Promotes Emt Via Downregulation Of E-cadherin Expressionmentioning

confidence: 99%

Section: Therapeutic Potential Of Rap1 Signaling In Cancersmentioning

confidence: 99%

See 2 more Smart Citations

The Role of Ras-Associated Protein 1 (Rap1) in Cancer: Bad Actor or Good Player?

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Though the TNM stage is vital and useful, it may be inadequate that it takes into account only some of the factors associated with the tumor itself, such as the depth of tumor invasion, numbers of lymph nodes and whether it has distant metastasis. As is known to us all, when patients are at the same TNM stage, their prognosis usually varies widely (Zhao and Chen, 2015;Gao et al, 2018). The nomogram or a web-based calculator is a multivariable model that considers multiple prognostic factors simultaneously, which is more suitable for the study of multivariable effects in large data sets to accurately predict the prognosis of cancer patients (Ullman et al, 2015;Jorissen et al, 2019;Hu et al, 2020;Jehi et al, 2020;Kim et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

A Prognostic Nomogram and Web-based Real-Time Calculator for Predicting CSS and OS of Primary Rectal Adenocarcinoma Patients

Wang¹,

Yang²,

Jing³

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundThe purpose of this study was to construct a clinical prognostic model of primary rectal adenocarcinoma (RAC) to assist in clinical diagnosis and treatment. MethodsPrimary RAC patients from 2010 to 2015 were selected from the surveillance, epidemiology and end results (SEER). The relevant significant variables were used to develop the prognosis model. A score was determined for each prognostic factor in the model. The Kaplan–Meier method and the log-rank test were used to establish and distinguish the survival curves. The accuracy of predictive model was assessed by receiver operating characteristics (ROCs) curve, concordance index (C-index), and decision curve analysis (DCA). ResultsA total of 8069 primary RAC were retrieved in this study. The overall survival（OS）model was established based on 14 variables. The CSS nomogram were constructed using 12 variables. The C-indexes for the training set of OS and CSS were 0.769 (95% confidence interval (CI) 0.761–0.777) and 0.793 (95% CI 0.784–0.802) respectively. The C-indexes for the validation set of OS and CSS were 0.776 (95% CI 0.768–0.784) and 0.794 (95% CI 0.785–0.803) respectively. High-quality calibration plots were observed and the model displayed a favorable outcome compared with (TNM) stage and SEER stage of primary RAC based on DCA curve. We then divided the patients into low-risk, medium-risk, and high-risk groups, showing that patients with primary RAC in the high-risk group had a poor prognosis. A primary RAC prognosis prediction model has been shown by a predicted nomogram for 3 or 5 years and a real-time web-based calculator. ConclusionsIn conclusion, we established a clinical prognosis model for primary RAC for the first time based on a variety of risk factors including individual differences, tumor-related factors, and diagnostic and therapeutic factors, which is more effective than TNM stage in predicting the prognosis of patients. The clinical prediction model visualized by the nomogram for 3 and 5 years and the web-based real-time calculator are helpful to optimize clinical work, facilitate patient consultation and clinical individualized treatment.

show abstract

TWEAK Signaling‐Induced ID1 Expression Drives Malignant Transformation of Hepatic Progenitor Cells During Hepatocarcinogenesis

et al. 2023

View full text Add to dashboard Cite

The malignant transformation of hepatic progenitor cells (HPCs) in the inflammatory microenvironment is the root cause of hepatocarcinogenesis. However, the potential molecular mechanisms are still elusive. The HPCs subgroup is identified by single‐cell RNA (scRNA) sequencing and the phenotype of HPCs is investigated in the primary HCC model. Bulk RNA sequencing (RNA‐seq) and proteomic analyses are also performed on HPC‐derived organoids. It is found that tumors are formed from HPCs in peritumor tissue at the 16th week in a HCC model. Furthermore, it is confirmed that the macrophage‐derived TWEAK/Fn14 promoted the expression of inhibitor of differentiation‐1 (ID1) in HPCs via NF‐κB signaling and a high level of ID1 induced aberrant differentiation of HPCs. Mechanistically, ID1 suppressed differentiation and promoted proliferation in HPCs through the inhibition of HNF4α and Rap1GAP transcriptions. Finally, scRNA sequencing of HCC patients and investigation of clinical specimens also verified that the expression of ID1 is correlated with aberrant differentiation of HPCs into cancer stem cells, patients with high levels of ID1 in HPCs showed a poorer prognosis. This study provides important intervention targets and a theoretical basis for the clinical diagnosis and treatment of HCC.

show abstract

The downregulation of Rap1 GTPase-activating protein is associated with a poor prognosis in colorectal cancer and may impact on tumor progression

Cited by 11 publications

References 36 publications

The Role of Ras-Associated Protein 1 (Rap1) in Cancer: Bad Actor or Good Player?

The Role of Ras-Associated Protein 1 (Rap1) in Cancer: Bad Actor or Good Player?

A Prognostic Nomogram and Web-based Real-Time Calculator for Predicting CSS and OS of Primary Rectal Adenocarcinoma Patients

TWEAK Signaling‐Induced ID1 Expression Drives Malignant Transformation of Hepatic Progenitor Cells During Hepatocarcinogenesis

Contact Info

Product

Resources

About