LW-213 induces G2/M cell cycle arrest through AKT/GSK3β/β-catenin signaling pathway in human breast cancer cells

Zhao, Li; Hua, Miao; Li, Wenjun; Sun, Yang; Huang, Shaoliang; Li, Zhiyu; Guo, Qinglong

doi:10.1002/mc.22321

Cited by 36 publications

(26 citation statements)

References 43 publications

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“…It has been demonstrated that there exists crosstalk between the Wnt/β-catenin signalling pathway and several other signalling pathways in breast cancer, including those involving MAPKs and Akt, suggesting inhibition of β-catenin may depend on MAPKs and/or Akt signalling [25, 26]. Indeed, PLCD1 induces cell cycle arrest by inhibiting Akt signalling in ESCC [6], and suppresses EMT through ERK signalling in KRAS-mutated colorectal cancers [7].…”

Section: Discussionmentioning

confidence: 99%

Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β- catenin/MMP7 signalling

et al. 2017

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Phospholipase C δ1 (PLCD1) encodes an enzyme involved in energy metabolism, calcium homeostasis and intracellular movement. It is located at 3p22 in a region that is frequently deleted in multiple cancers, and the PLCD1 enzyme is a potential tumour suppressor in breast cancer that inhibits matrix metalloprotease (MMP) 7, but the detailed mechanism remains elusive. In this study, we found that PLCD1 was downregulated in breast cancers, and the gain-or-loss functional assay revealed that PLCD1 inhibited cell migration and invasion in vitro via the ERK1/2/β-catenin/MMP7 signalling pathway. Furthermore, KIF3A was identified as a downstream mediator of PLCD1, and there was an inverse correlation between the expression of PLCD1 and KIF3A. Knockdown of KIF3A expression alone suppressed cell migration and invasion, and attenuated ERK1/2/β-catenin/MMP7 signalling that was reactivated by knocking down PLCD1 in vitro. Collectively, our findings suggest that PLCD1 acts as a tumour suppressor, by KIF3A-mediated suppression of ERK1/2/β-catenin/MMP7 signalling, at least in part, in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β- catenin/MMP7 signalling

et al. 2017

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“…In the absence of Wnt, cytoplasmic β-catenin is phosphorylated on several serine and threonine residues by a destruction complex containing GSK3β, casein kinase1 (CK1), axin and adenomatous polyposis coli (APC), which leads to ubiquitin-proteasome-mediated degradation of β-catenin [27, 55]. Lithium chloride (LiCl) is known to activate canonical Wnt signaling by inhibiting GSK3β and consequently stabilizing free cytosolic β-catenin [56, 57]. Coincidently, in our study we found that depletion of polyamine induced by SSAT over-expression decreased p-GSK3β expression and inhibited β-catenin nuclear translocation in hepatocellular and colorectal carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasisviaAKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells

et al. 2016

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Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are among the most common cancers across the world. Therefore, identifying the potential molecular mechanisms that promote HCC and CRC progression and metastasis are urgently needed. Spermidine/spermine N1-acetyltransferase (SSAT) is a catabolic enzyme that acetylates the high-order polyamines spermine and spermidine, thus decreasing the cellular content of polyamines. Several publications have suggested that depletion of intracellular polyamines inhibited tumor progression and metastasis in various cancer cells. However, whether and how SSAT regulates cell growth, migration and invasion in hepatocellular and colorectal carcinoma cells remains unclear. In this study, depletion of polyamines mediated by SSAT not only attenuated the tumor cell proliferation but also dramatically inhibited cell migration and invasion in hepatocellular and colorectal carcinoma cells. Subsequent investigations revealed introduction of SSAT into HepG2, SMMC7721 hepatocellular carcinoma cells and HCT116 colorectal carcinoma cells significantly suppressed p-AKT, p-GSK3β expression as well as β-catenin nuclear translocation, while inhibition of GSK3β activity or exogenous polyamines could restore SSAT-induced decreases in the protein expression of p-AKT, p-GSK3β and β-catenin. Conversely, knockdown of SSAT in Bel7402 hepatocellular carcinoma cells and HT-29 colorectal carcinoma cells which expressed high levels of SSAT endogenously significantly promoted the expression of p-AKT, p-GSK3β as well as β-catenin nuclear translocation. Taken together, our results indicated depletion of polyamines by SSAT significantly inhibited cell proliferation, migration and invasion through AKT/GSK3β/β-catenin signaling pathway in hepatocellular carcinoma and colorectal cancer cells.

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“…GSK-3β also functions as a tumor suppressor, because GSK3β can suppress the Wnt/β-catenin pathway by phosphorylating β-catenin [40]. Moreover, β-catenin transactivation has been associated with cyclin D1 overexpression in breast cancer [46].…”

Section: Discussionmentioning

confidence: 99%

Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGFβ-Induced EMT in Ovarian Cancer

et al. 2016

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The compound fuling granule (CFG) is a traditional Chinese drug which has been used to treat ovarian cancer in China for over twenty years. Nevertheless, the underlying molecular mechanism of its anti-cancer effect remains unclear. In this study, microarray data analysis was performed to search differentially expressed genes in CFG-treated ovarian cancer cells. Several cell cycle and epithelial-mesenchymal transition (EMT) related genes were identified. The microarray analyses also revealed that CFG potentially regulates EMT in ovarian cancer. We also found that, functionally, CFG significantly suppresses ovarian cancer cell proliferation by cell cycle arrest, apoptosis and senescence and the AKT/GSK-3β pathway is possibly involved. Additionally, the invasion and migration ability of ovarian cancer induced by TGFβ is significantly suppressed by CFG. In conclusion, our results demonstrated that CFG suppresses ovarian cancer cell proliferation as well as TGFβ1-induced EMT in vitro. Finally, we discovered that CFG suppresses tumor growth and distant metastasis in vivo. Overall, these findings provide helpful clues to design novel clinical treatments against cancer.

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LW-213 induces G2/M cell cycle arrest through AKT/GSK3β/β-catenin signaling pathway in human breast cancer cells

Cited by 36 publications

References 43 publications

Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β- catenin/MMP7 signalling

Phospholipase Cδ1 suppresses cell migration and invasion of breast cancer cells by modulating KIF3A-mediated ERK1/2/β- catenin/MMP7 signalling

Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasisviaAKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells

Fuling Granule, a Traditional Chinese Medicine Compound, Suppresses Cell Proliferation and TGFβ-Induced EMT in Ovarian Cancer

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