scholarly journals A double-negative feedback loop between EZH2 and miR-26a regulates tumor cell growth in hepatocellular carcinoma

2016 ◽  
Vol 48 (3) ◽  
pp. 1195-1204 ◽  
Author(s):  
CHUNBO ZHUANG ◽  
PEI WANG ◽  
DA HUANG ◽  
LUMING XU ◽  
XIAOBEI WANG ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Tumor Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Double Negative ◽  
Tumor Cell Growth

scholarly journals HIC1 and miR-23~27~24 clusters form a double-negative feedback loop in breast cancer

2016 ◽  
Vol 24 (3) ◽  
pp. 421-432 ◽  
Author(s):  
Yanbo Wang ◽  
Hongwei Liang ◽  
Geyu Zhou ◽  
Xiuting Hu ◽  
Zhengya Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Double Negative

scholarly journals A GYS2/p53 Negative Feedback Loop Restricts Tumor Growth in HBV-Related Hepatocellular Carcinoma

2018 ◽  
Vol 79 (3) ◽  
pp. 534-545 ◽  
Author(s):  
Shi-Lu Chen ◽  
Chris Zhiyi Zhang ◽  
Li-Li Liu ◽  
Shi-Xun Lu ◽  
Ying-Hua Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop

scholarly journals Multistability and consequent phenotypic plasticity in AMPK-Akt double negative feedback loop in cancer cells

2020 ◽  
Author(s):  
Adithya Chedere ◽  
Kishore Hari ◽  
Saurav Kumar ◽  
Annapoorni Rangarajan ◽  
Mohit Kumar Jolly
Keyword(s):  
Breast Cancer ◽  
Phenotypic Plasticity ◽  
Cancer Cells ◽  
Cell Population ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Phenotypic Switching ◽  
Negative Feedback Loop ◽  
Double Negative ◽  
Protein Levels

AbstractAdaptation and survival of cancer cells to various stress and growth factor conditions is crucial for successful metastasis. A double-negative feedback loop between two serine/threonine kinases AMPK and Akt can regulate the adaptation of breast cancer cells to matrix-deprivation stress. This feedback loop can generate majorly two phenotypes or cell states: matrix detachment-triggered pAMPKhigh/ pAktlow state, and matrix (re)attachment-triggered pAkthigh/ pAMPKlow state. However, whether these two cell states can exhibit phenotypic plasticity and heterogeneity in a given cell population, i.e., whether they can co-exist and undergo spontaneous switching to generate the other subpopulation, remains unclear. Here, we develop a mechanism-based mathematical model that captures the set of experimentally reported interactions among AMPK and Akt. Our simulations suggest that the AMPK-Akt feedback loop can give rise to two co-existing phenotypes (pAkthigh/ pAMPKlow and pAMPKhigh/pAktlow) in specific parameter regimes. Next, to test the model predictions, we segregated these two subpopulations in MDA-MB-231 cells and observed that each of them was capable of switching to another in adherent conditions. Finally, the predicted trends are supported by clinical data analysis of TCGA breast cancer and pan-cancer cohorts that revealed negatively correlated pAMPK and pAkt protein levels. Overall, our integrated computational-experimental approach unravels that AMPK-Akt feedback loop can generate multistability and drive phenotypic switching and heterogeneity in a cancer cell population.

scholarly journals KLF2 inhibits TGF-β-mediated cancer cell motility in hepatocellular carcinoma

2020 ◽  
Vol 52 (5) ◽  
pp. 485-494 ◽  
Author(s):  
Yining Li ◽  
Shuo Tu ◽  
Yi Zeng ◽  
Cheng Zhang ◽  
Tian Deng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Motility ◽  
Cancer Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Negative Feedback Loop ◽  
Liver Malignancy ◽  
Cancer Cell Motility

Abstract Feedback regulation plays a pivotal role in determining the intensity and duration of TGF-β signaling and subsequently affecting the pathophysiological roles of TGF-β, including those in liver malignancy. KLF2, a member of the Krüppel-like factor (KLF) family transcription factors, has been implicated in impeding hepatocellular carcinoma (HCC) development. However, the underlying molecular mechanisms are not fully understood. In the present study, we found that TGF-β stimulates the expression of KLF2 gene in several HCC cell lines. KLF2 protein is able to inhibit TGF-β/Smad signaling in HCC cells as assessed by luciferase reporter assay. Further studies indicated that KLF2 inhibits the transcriptional activity of Smad2/3 and Smad4 and ameliorates TGF-β-induced target gene expression, therefore creating a novel negative feedback loop in TGF-β signaling. Functionally, stably expression of KLF2 in HCCLM3 cells attenuated TGF-β-induced cancer cell motility in wound-healing and transwell assays by interfering with TGF-β-mediated upregulation of MMP2. Together, our results revealed that KLF2 protein has a tumor-suppressive function in HCC through a negative feedback loop over TGF-β signaling.

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