RNF6 promotes colorectal cancer invasion and migration via the Wnt/β-catenin pathway by inhibiting GSK3β activity

Li, Qiken; Wang, Gang; Tao, Jinhua; Chen, Weiping

doi:10.1016/j.prp.2021.153545

Cited by 9 publications

(7 citation statements)

References 31 publications

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“…Furthermore, the overexpression of NSD3 was observed in cancer types including colorectal cancer and it enhances the phosphorylation levels of ERK1/2 in CRC cell lines [ 51 , 52 ]. Last, RNF6 amplification was frequently observed in CRC, linked to cancer progression and metastasis [ 53 , 54 ] as well as an increase in the phosphorylation levels of ERK1 in cervical cancer [ 55 ]. To assess whether the genomic amplification of CCNE1 , NSD3 , RNF6 genes were reflected in increased mRNA expression, we performed real time RT-PCR.…”

Section: Resultsmentioning

confidence: 99%

Investigation of evolutionary dynamics for drug resistance in 3D spheroid model system using cellular barcoding technology

Yalcin,

Yilmaz,

Dilber

et al. 2023

PLoS ONE

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Complex evolutionary dynamics governing the drug resistance is one of the major challenges in cancer treatment. Understanding these mechanisms requires a sequencing technology with higher resolution to delineate whether pre-existing or de novo drug mechanisms are behind the drug resistance. Combining this technology with clinically very relevant model system, namely 3D spheroids, better mimicking tumorigenesis and drug resistance have so far been lacking. Thus, we sought to establish dabrafenib and irinotecan resistant derivatives of barcoded 3D spheroids with the ultimate aim to quantify the selection-induced clonal dynamics and identify the genomic determinants in this model system. We found that dabrafenib and irinotecan induced drug resistance in 3D-HT-29 and 3D-HCT-116 spheroids are mediated by pre-existing and de novo resistant barcodes, indicating the presence of polyclonal drug resistance in this system. Moreover, whole-exome sequencing analysis found chromosomal gains and mutations associated with dabrafenib and irinotecan resistance in 3D-HT-29 and 3D-HCT-116 spheroids. Last, we show that dabrafenib and irinotecan resistance are also mediated by multiple drug resistance by detection of upregulation of the drug efflux pumps, ABCB1 and ABCG2, in our spheroid model system. Overall, we present the quantification of drug resistance and evolutionary dynamics in spheroids for the first time using cellular barcoding technology and the underlying genomic determinants of the drug resistance in our model system.

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Section: Resultsmentioning

confidence: 99%

Investigation of evolutionary dynamics for drug resistance in 3D spheroid model system using cellular barcoding technology

Yalcin,

Yilmaz,

Dilber

et al. 2023

PLoS ONE

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“…7A ). In addition, GSK3β has been found to exhibit a key role in the development of human cancers such as breast cancer, colorectal cancer, and PC [ 31 – 33 ]. RT-qPCR result showed that GSK3β level was notably downregulated in PC tissues compared to normal tissues (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Cancer associated fibroblasts secreted exosomal miR-1290 contributes to prostate cancer cell growth and metastasis via targeting GSK3β

Wang

Cao

et al. 2022

Cell Death Discov.

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Cancer-associated fibroblasts (CAFs) play crucial roles in mediating tumor growth and metastasis via transferring exosomes to neighboring cells, whereas the mechanisms by which CAFs regulate the tumorgenesis of prostate cancer (PC) remain largely unknown. In this study, CAFs and normal fibroblasts (NFs) were isolated from PC tissues and adjacent normal tissues, respectively. Exosomes (NFs-Exo and CAFs-Exo) were then isolated from the supernatant of NFs and CAFs. Next, the differentially expressed miRNAs (DEMs) between NFs-Exo and CAFs-Exo were identified using RNA-sequencing. Cell viability, migration and invasion were detected with CCK-8 and Transwell assays. Protein expression was measured with western blot. We found that CAFs-Exo remarkably enhanced PC cell migration, invasion, stemness, epithelial-mesenchymal transition (EMT) and metastasis. Significantly, miR-1290 level was upregulated in CAFs-Exo compared to NFs-Exo. In addition, CAFs could transfer exosomes to PC cells, resulting in a marked increase of miR-1290 level in cells. Moreover, exosomal miR-1290 could inhibit GSK3β/β-catenin signaling by binding with the downstream target GSK3β mRNA. Meanwhile, miR-1290 antagomir notably reversed the effects of CAFs-Exo on PC cells through activating GSK3β/β-catenin signaling. Collectively, exosomal miR-1290 from CAFs could promote PC cell growth and metastasis via inhibiting GSK3β/β-catenin signaling, suggesting that miR-1290 may serve as potential therapeutic target for the treatment of PC.

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“…To verify the above conjecture, we used in this study IM-12, a specific agonist of the Wnt signaling pathway that was reported to specifically inhibit the expression of GSK-3β while increasing the expression of β-catenin and downstream proteins [ 51 , 79 , 80 ]. In this study, it was observed that pre-treatment with CGA partially suppressed the expression of core proteins associated with the Wnt signaling pathway activated by IM-12, such as β-catenin, p-GSK-3β, and c-Myc, while concurrently partially increasing the expression of GSK-3β ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

Chlorogenic Acid Attenuates Isoproterenol Hydrochloride-Induced Cardiac Hypertrophy in AC16 Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway

He,

Wang,

et al. 2024

Molecules

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Cardiac hypertrophy (CH) is an important characteristic in heart failure development. Chlorogenic acid (CGA), a crucial bioactive compound from honeysuckle, is reported to protect against CH. However, its underlying mechanism of action remains incompletely elucidated. Therefore, this study aimed to explore the mechanism underlying the protective effect of CGA on CH. This study established a CH model by stimulating AC16 cells with isoproterenol (Iso). The observed significant decrease in cell surface area, evaluated through fluorescence staining, along with the downregulation of CH-related markers, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) at both mRNA and protein levels, provide compelling evidence of the protective effect of CGA against isoproterenol-induced CH. Mechanistically, CGA induced the expression of glycogen synthase kinase 3β (GSK-3β) while concurrently attenuating the expression of the core protein β-catenin in the Wnt/β-catenin signaling pathway. Furthermore, the experiment utilized the Wnt signaling activator IM-12 to observe its ability to modulate the impact of CGA pretreatment on the development of CH. Using the Gene Expression Omnibus (GEO) database combined with online platforms and tools, this study identified Wnt-related genes influenced by CGA in hypertrophic cardiomyopathy (HCM) and further validated the correlation between CGA and the Wnt/β-catenin signaling pathway in CH. This result provides new insights into the molecular mechanisms underlying the protective effect of CGA against CH, indicating CGA as a promising candidate for the prevention and treatment of heart diseases.

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RNF6 promotes colorectal cancer invasion and migration via the Wnt/β-catenin pathway by inhibiting GSK3β activity

Cited by 9 publications

References 31 publications

Investigation of evolutionary dynamics for drug resistance in 3D spheroid model system using cellular barcoding technology

Investigation of evolutionary dynamics for drug resistance in 3D spheroid model system using cellular barcoding technology

Cancer associated fibroblasts secreted exosomal miR-1290 contributes to prostate cancer cell growth and metastasis via targeting GSK3β

Chlorogenic Acid Attenuates Isoproterenol Hydrochloride-Induced Cardiac Hypertrophy in AC16 Cells by Inhibiting the Wnt/β-Catenin Signaling Pathway

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