Krüppel-like Factor 4 Suppresses Serine/Threonine Kinase 33 Activation and Metastasis of Gastric Cancer through Reversing Epithelial–Mesenchymal Transition

Kong, Fanyang; Sun, Tao; Kong, Xiangyu; Xie, Dacheng; Li, Zhao‐Shen; Xie, Keping

doi:10.1158/1078-0432.ccr-17-3346

Cited by 33 publications

(33 citation statements)

References 34 publications

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“…In addition, decreased KLF4 expression and increased Sp1 expression was a novel molecular mechanism of FOXM1c overexpression and that FOXM1c promoted cancer invasion and metastasis in human pancreatic cancer 19 . Krüppel‐like factor 4 played a negative role in gastric cancer cell invasion, which was reversed by upregulation of serine/threonine kinase 33 expression at the transcriptional level 20 . Our previous studies found that loss of KLF4 expression contributed to enhance human gastric cancer EMT and metastasis development and progression through regulating PODXL 21 .…”

Section: Introductionmentioning

confidence: 98%

GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

et al. 2020

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| 1203 wileyonlinelibrary.com/journal/cas | INTRODUC TI ONColorectal cancer is the third most common tumor and the third leading cause of cancer-related death in man and women in the world. 1,2 In China, there was an increase of over 376 300 cases of CRC and a total of 191 000 deaths during 2015. 3 Environmental and lifestyle changes, including an altered diet, lack of appropriate physical activity, circadian disruption, and increase in alcohol consumption, have enormously aggravated the burden of CRC. 4 In the past several years, the incidence and mortality of CRC increased rapidly and the onset age was muchThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractGINS complex subunit 4 (GINS4) is essential for DNA replication initiation and elongation in the G 1 /S phase cell cycle in eukaryotes, however, its functional roles and molecular mechanisms remain unclear in many aspects. Our study was designed to investigate the clinical significance, biological function, and molecular mechanism of GINS4 in colorectal cancer (CRC). First, we confirmed that GINS4 expression was significantly overexpressed in CRC cells and tissues. The immunohistochemical results in tissue microarray from 106 CRC patients showed that a high level of GINS4 expression was positively correlated with advanced T stage, higher tumor TNM stage, and poor differentiation. The results from univariate and multivariate survival analysis models based on 106 CRC patients revealed that GINS4 might serve as an independent prognostic indicator for overall survival and disease-free survival of CRC patients.Moreover, downregulated GINS4 can inhibit growth and the cell cycle and accelerate cell apoptosis progression in vitro as well as inhibit tumorigenesis in vivo. Besides, our results also indicated that Krüppel-like factor 4 (KLF4) can negatively regulate GINS4 expression at the transcriptional level and the KLF/GINS4 pathway might play a vital role in the growth and prognosis of CRC. K E Y W O R D Sbiomarker, colorectal cancer, GINS4, growth, KLF4

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Section: Introductionmentioning

confidence: 98%

GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

et al. 2020

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“…Gastric cancer (GC) is a major public health problem, ranking the fourth most frequently diagnosed cancer and the second in cancer-associated death worldwide [1]. Although the diagnosis and treatment of GC have been improved, the 5-year overall survival rate of GC remains poor, largely due to diagnostics in advanced stages [2,3].…”

Section: Introductionmentioning

confidence: 99%

miR-204-5p Suppress Lymph Node Metastasis via Regulating CXCL12 and CXCR4 in Gastric Cancer

Zhang¹,

Xing²,

Xu³

et al. 2020

J. Cancer

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Gastric cancer (GC) exhibits a poor prognosis due to extensive invasion and lymphatic metastasis in the advanced stage. In this study, we firstly found that the expression of miR-204-5p markedly decreased in GC patients' tissue and serum, especially in GC with lymphatic metastasis. And ROC analysis showed miR-204-5p also served as a predicted factor for the lymphatic metastasis of GC. CXCL12 and CXCR4 were predicted and confirmed as the functional targets of miR-204-5p by Targetscan analysis, dual luciferase assay and western blotting analysis. In addition, we further determined that miR-204-5p suppresses migration and invasion in GC. This finding elucidates new functions and mechanisms for miR-204-5p in GC development and provides a new potential diagnostic marker and therapeutic targets for GC.

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“…Krüppel‐like transcription factor (KLF4) is a zinger transcription factor and plays a criterial role in regulating cell proliferation, differentiation, apoptosis, and migration . KLF4 has been found to act as an oncogene or tumor suppressor gene in different cancers in a context‐dependent manner .…”

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori CagA promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR‐155/KLF4 signaling pathway

Ren

Zhao

et al. 2019

Molecular Carcinogenesis

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The Helicobacter pylori (H. pylori) cytotoxin-associated gene A (CagA) and Krüppel-like transcription factor (KLF4) were both closely associated with the development and progression of gastric cancer (GC). However, the nature of the interactions between CagA and KLF4 in GC development has not been elucidated. Therefore, we focused on the CagA-mediated promotion of the malignant transformation of gastric epithelial cells. Herein, we first examined the expression of KLF4 in both human cancer and paracarcinoma tissues with or without H. pylori infection and found that KLF4 expression was significantly decreased in H. pylori-positive GC cells compared with the H. pylori-negative GC cells. Further functional studies revealed that the increased expression of CagA could suppress KLF4 expression and promote the malignant transformation of normal epithelial cells. Subsequently, we found that CagA could upregulate miR-155 and further restrict the expression of downstream KLF4. More importantly, the overexpression of miR-155 in GES-1 promoted epithelial-mesenchymal transition and eventually facilitated tumor growth in vivo. Overall, the identification of the CagA/miR-155/KLF4 signaling pathway provided a new insight into the development and treatment of GC. K E Y W O R D S CagA, gastric cancer, Helicobacter pylori, Krüppel-like factor 4, miR-155

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Krüppel-like Factor 4 Suppresses Serine/Threonine Kinase 33 Activation and Metastasis of Gastric Cancer through Reversing Epithelial–Mesenchymal Transition

Cited by 33 publications

References 34 publications

GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

GINS complex subunit 4, a prognostic biomarker and reversely mediated by Krüppel‐like factor 4, promotes the growth of colorectal cancer

miR-204-5p Suppress Lymph Node Metastasis via Regulating CXCL12 and CXCR4 in Gastric Cancer

Helicobacter pylori CagA promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR‐155/KLF4 signaling pathway

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