A Positive Feedback Loop Regulates the Expression of Polycomb Group Protein BMI1 via WNT Signaling Pathway

AbstractThe leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) is considered to be a stem cell marker in many normal tissues and promotes tissue development, regeneration, and repair. LGR6 is also related to the initiation and progression of some malignant tumors. However, the role of LGR6 in cervical cancer has not been reported. Here, immunohistochemistry and western blotting showed that LGR6 was significantly upregulated in cervical cancer, compared with the normal cervix. By analyzing The Cancer Genome Atlas database, LGR6 was found to be correlated with a poor prognosis of cervical cancer. Then, a small population of LGR6high cells isolated by using the fluorescence-activated cell sorting exhibited enhanced properties of cancer stem cells including self-renewal, differentiation, and tumorigenicity. Moreover, RNA sequencing revealed that LGR6 was correlated with the Wnt signaling pathway and TOP/FOP, reverse transcription-PCR, and western blotting further proved that LGR6 could activate the Wnt/β-catenin signaling pathway. Interestingly, LGR6 upregulated the expression of TCF7L2 by activating the Wnt/β-catenin pathway. Then, TCF7L2 combining with β-catenin in the nucleus enhanced LGR6 transcription by binding the promoter of LGR6, which further activated the Wnt signaling to form a positive feedback loop. Thus, our study demonstrated that LGR6 activated a novel β-catenin/TCF7L2/LGR6-positive feedback loop in LGR6high cervical cancer stem cells (CSCs), which provided a new therapeutic strategy for targeting cervical CSCs to improve the prognosis of cervical cancer patients.

Download Full-text

The Dickkopf1 and FOXM1 positive feedback loop promotes tumor growth in pancreatic and esophageal cancers

Oncogene ◽

10.1038/s41388-021-01860-z ◽

2021 ◽

Author(s):

Hirokazu Kimura ◽

Ryota Sada ◽

Naoki Takada ◽

Akikazu Harada ◽

Yuichiro Doki ◽

...

Keyword(s):

Cell Proliferation ◽

Wnt Signaling ◽

Cancer Cell ◽

Positive Feedback ◽

Feedback Loop ◽

Ductal Adenocarcinoma ◽

Cancer Cell Proliferation ◽

Positive Feedback Loop ◽

Dkk1 Expression ◽

Foxm1 Expression

AbstractDickkopf1 (DKK1) is overexpressed in various cancers and promotes cancer cell proliferation by binding to cytoskeleton-associated protein 4 (CKAP4). However, the mechanisms underlying DKK1 expression are poorly understood. RNA sequence analysis revealed that expression of the transcription factor forkhead box M1 (FOXM1) and its target genes concordantly fluctuated with expression of DKK1 in pancreatic ductal adenocarcinoma (PDAC) cells. DKK1 knockdown decreased FOXM1 expression and vice versa in PDAC and esophageal squamous cell carcinoma (ESCC) cells. Inhibition of either the DKK1-CKAP4-AKT pathway or the ERK pathway suppressed FOXM1 expression, and simultaneous inhibition of both pathways showed synergistic effects. A FOXM1 binding site was identified in the 5ʹ-untranslated region of the DKK1 gene, and its depletion decreased DKK1 expression and cancer cell proliferation. Clinicopathological and database analysis revealed that PDAC and ESCC patients who simultaneously express DKK1 and FOXM1 have a poorer prognosis. Multivariate analysis demonstrated that expression of both DKK1 and FOXM1 is the independent prognostic factor in ESCC patients. Although it has been reported that FOXM1 enhances Wnt signaling, FOXM1 induced DKK1 expression independently of Wnt signaling in PDAC and ESCC cells. These results suggest that DKK1 and FOXM1 create a positive feedback loop to promote cancer cell proliferation.

Download Full-text

miR-29 Modulates Wnt Signaling in Human Osteoblasts through a Positive Feedback Loop

Journal of Biological Chemistry ◽

10.1074/jbc.m110.116137 ◽

2010 ◽

Vol 285 (33) ◽

pp. 25221-25231 ◽

Cited By ~ 264

Author(s):

Kristina Kapinas ◽

Catherine Kessler ◽

Tinisha Ricks ◽

Gloria Gronowicz ◽

Anne M. Delany

Keyword(s):

Wnt Signaling ◽

Positive Feedback ◽

Feedback Loop ◽

Positive Feedback Loop ◽

Human Osteoblasts

Download Full-text

P2.01-17 MALAT1-Mir-101-SOX9 Feedback Loop Modulates the Chemo-Resistance of Lung Cancer Cell to DDP via Wnt Signaling Pathway

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2018.08.1071 ◽

2018 ◽

Vol 13 (10) ◽

pp. S671

Author(s):

W. Chen

Keyword(s):

Lung Cancer ◽

Wnt Signaling ◽

Signaling Pathway ◽

Cancer Cell ◽

Feedback Loop ◽

Wnt Signaling Pathway ◽

Lung Cancer Cell

Download Full-text

SNHG1/miR‐556‐5p/TCF12 feedback loop enhances the tumorigenesis of meningioma through Wnt signaling pathway

Journal of Cellular Biochemistry ◽

10.1002/jcb.29423 ◽

2019 ◽

Vol 121 (2) ◽

pp. 1880-1889 ◽

Cited By ~ 3

Author(s):

Yubing Zhang ◽

Runze Yu ◽

Qingsong Li ◽

Yong Li ◽

Tao Xuan ◽

...

Keyword(s):

Wnt Signaling ◽

Signaling Pathway ◽

Feedback Loop ◽

Wnt Signaling Pathway

Download Full-text

APP/PS1 Gene-Environment Noise Interaction Aggravates AD-like Neuropathology in Hippocampus Via Activation of the VDAC1 Positive Feedback Loop

Current Alzheimer Research ◽

10.2174/1567205018666210324114153 ◽

2021 ◽

Vol 18 (1) ◽

pp. 14-24

Author(s):

Huimin Chi ◽

Qingfeng Zhai ◽

Ming Zhang ◽

Donghong Su ◽

Wa Cao ◽

...

Keyword(s):

Signaling Pathway ◽

Positive Feedback ◽

Feedback Loop ◽

Noise Exposure ◽

Glycogen Synthase ◽

Amyloid Β ◽

Environmental Noise ◽

Voltage Dependent Anion Channel ◽

Positive Feedback Loop ◽

The Impact

Background: Environmental risk factors, including environmental noise stress, and genetic factors, have been associated with the occurrence and development of Alzheimer’s disease (AD). However, the exact role and mechanism of AD-like pathology induced by environment-gene interactions between environmental noise and APP/PS1 gene remain elusive. Methods: Herein, we investigated the impact of chronic noise exposure on AD-like neuropathology in APP/PS1 transgenic mice. The Morris water maze (MWM) task was conducted to evaluate AD-like changes. The hippocampal phosphorylated Tau, amyloid-β (Aβ), and neuroinflammation were assessed. We also assessed changes in positive feedback loop signaling of the voltage-dependent anion channel 1 (VDAC1) to explore the potential underlying mechanism linking AD-like neuropathology to noise-APP/PS1 interactions. Results: Long-term noise exposure significantly increased the escape latency and the number of platform crossings in the MWM task. The Aβ overproduction was induced in the hippocampus of APP/PS1 mice, along with the increase of Tau phosphorylation at Ser396 and Thr231 and the increase of the microglia and astrocytes markers expression. Moreover, the VDAC1-AKT (protein kinase B)-GSK3β (glycogen synthase kinase 3 beta)-VDAC1 signaling pathway was abnormally activated in the hippocampus of APP/PS1 mice after noise exposure. Conclusion: Chronic noise exposure and APP/PS1 overexpression may synergistically exacerbate cognitive impairment and neuropathological changes that occur in AD. This interaction may be mediated by the positive feedback loop of the VDAC1-AKT-GSK3β-VDAC1 signaling pathway.

Download Full-text