Suppression of synuclein gamma inhibits the movability of endometrial carcinoma cells by PI3K/AKT/ERK signaling pathway

Ni, Man; Zhao, Yue; Wang, Xiaoguang

doi:10.1007/s13258-021-01080-5

Cited by 6 publications

(5 citation statements)

References 30 publications

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“…In addition, Ca 2+ is an important messenger in the activation of this signalling pathway 27,28 . Hence, our findings suggest that subvacuum dressings provide a subvacuum environment for wounds, which is conducive to Ca 2+ influx, activation of the PI3K/AKT1 signalling pathway, and regulation of the cytoskeleton 29,30 . This study confirmed that the intracellular Ca 2+ concentration increased significantly at 4 h under a subvacuum environment.…”

Section: Discussionsupporting

confidence: 83%

“…27,28 Hence, our findings suggest that subvacuum dressings provide a subvacuum environment for wounds, which is conducive to Ca 2+ influx, activation of the PI3K/ AKT1 signalling pathway, and regulation of the cytoskeleton. 29,30 This study confirmed that the intracellular Ca 2+ concentration increased significantly at 4 h under a subvacuum environment. Although the Ca 2+ concentration displayed a decreasing trend after reaching a peak at 24 h, it still remained above a normal level.…”

Section: Discussionsupporting

confidence: 76%

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Subvacuum environment‐enhanced cell migration promotes wound healing without increasing hypertrophic scars caused by excessive cell proliferation

et al. 2023

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Cell migration and proliferation are conducive to wound healing; however, regulating cell proliferation remains challenging, and excessive proliferation is an important cause of scar hyperplasia. Here, we aimed to explore how a subvacuum environment promotes wound epithelisation without affecting scar hyperplasia. Human immortalized keratinocyte cells and human skin fibroblasts were cultured under subvacuum conditions (1/10 atmospheric pressure), and changes in cell proliferation and migration, target protein content, calcium influx, and cytoskeleton and membrane fluidity were observed. Mechanical calcium (Ca2+) channel blockers were used to prevent Ca2+ influx for reverse validation. A rat wound model was used to elucidate the mechanism of the subvacuum dressing in promoting healing. The subvacuum environment was observed to promote cell migration without affecting cell proliferation; intracellular Ca2+ concentrations and PI3K, p‐PI3K, AKT1, p‐AKT 1 levels increased significantly. The cytoskeleton was depolymerized, pseudopodia were reduced or absent, and membrane fluidity increased. The use of Ca2+ channel blockers weakened or eliminated these changes. Animal experiments confirmed these phenomena and demonstrated that subvacuum dressings can effectively promote wound epithelisation. Our study demonstrates that the use of subvacuum dressings can enhance cell migration without affecting cell proliferation, promote wound healing, and decrease the probability of scar hyperplasia.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 76%

Subvacuum environment‐enhanced cell migration promotes wound healing without increasing hypertrophic scars caused by excessive cell proliferation

et al. 2023

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“…SNCG (γ-Synuclein gene), which is identified as breast cancer specific gene 1 (BCSG1), is upregulated in advanced breast cancers. SNCG leads to a sharp increase in cell motility and invasiveness in vitro, as well as a profound augmentation of metastasis in vivo in breast cancer, 49 SNCG siRNA could downregulate the expression of phosphorylation of AKT and ERK and then decrease the proliferation and migration in breast cancer cells, 30 , 50 and siSNCG treatment affected MCF7 and T47D breast cancer cells, which are 2 estrogen receptor-positive breast cancer cells. 51 A recent study reported that miRNA-15a mediated the cell cycle and induced apoptosis in breast cancer cells by targeting SNCG.…”

Section: Discussionmentioning

confidence: 99%

The Herbal Combination Shu Gan Jie Yu Regulates the SNCG/ER-a/AKT-ERK Pathway in DMBA-Induced Breast Cancer and Breast Cancer Cell Lines Based on RNA-Seq and IPA Analysis

Zhao,

Wang

et al. 2024

Integr Cancer Ther

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Background: Soothing the liver (called Shu Gan Jie Yu in Chinese, SGJY) is a significant therapeutic method for breast cancer in TCM. In this study, 3 liver-soothing herbs, including Cyperus rotundus L., Citrus medica L. var. sarcodactylis Swingle and Rosa rugosa Thunb. were selected and combined to form a SGJY herbal combinatory. The Aim of the Study: To investigate the inhibiting effect of SGJY on breast cancer in vivo and vitro, and to explore the potential mechanisms. Materials and Methods: SGJY herbal combination was extracted using water. A breast cancer rat model was developed by chemical DMBA by gavage, then treated with SGJY for 11 weeks. The tumor tissue was preserved for RNA sequencing and analyzed by IPA software. The inhibition effects of SGJY on MCF-7 and T47D breast cancer cells were investigated by SRB assay and cell apoptosis analysis, and the protein expression levels of SNCG, ER-α, p-AKT and p-ERK were measured by western blotting. Results: SGJY significantly reduced the tumor weight and volume, and the level of estradiol in serum. The results of IPA analysis reveal SGJY upregulated 7 canonical pathways and downregulated 16 canonical pathways. Estrogen receptor signaling was the key canonical pathway with 9 genes downregulated. The results of upstream regulator analysis reveal beta-estradiol was the central target; the upstream regulator network scheme showed that 86 genes could affect the expression of the beta-estradiol, including SNCG, CCL21 and MB. Additionally, SGJY was verified to significantly alter the expression of SNCG mRNA, CCL21 mRNA and MB mRNA which was consistent with the data of RNA-Seq. The inhibition effects of SGJY exhibited a dose-dependent response. The apoptosis rates of MCF7 and T47D cells were upregulated. The protein expression of SNCG, ER-α, p-AKT and p-ERK were all significantly decreased by SGJY on MCF-7 and T47D cells. Conclusion: The results demonstrate that SGJY may inhibit the growth of breast cancer. The mechanism might involve downregulating the level of serum estradiol, and suppressing the protein expression in the SNCG/ER-α/AKT-ERK pathway.

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“…Meanwhile, it is also proposed that the PI3K/AKT pathway is one of the most common pathways that is altered in EC: The molecular spectrum of EC suggests that the mutation rates of PI3KCA, PIK3R1 and AKT1 are 59.7, 33 and 3.2 m respectively in all cases ( 22 , 24 ). Previous studies illustrate that inhibiting the PI3K/AKT pathway greatly suppresses the proliferation, migration and invasion of EC cell lines ( 25 , 26 ). Moreover, it is reported that ITGA7 regulates PI3K/AKT ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Effect of integrin α7 on cell proliferation, invasion, apoptosis and the PI3K/AKT pathway, and its association with clinicopathological features in endometrial cancer

et al. 2022

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Targeting integrin α7 (ITGA7) suppresses malignant progression of several types of cancer, including tongue squamous cell carcinoma, hepatocellular carcinoma and non-small cell lung cancer, while the effect of its knockdown on cell function and its association with clinicopathological features in endometrial cancer (EC) is unclear. The present study aimed to investigate this issue. ITGA7 was knocked down by short-interfering (si)RNA in Ishikawa and RL95-2 cells followed by western blotting and reverse transcription-quantitative PCR assays. Subsequently, cell proliferation, apoptosis, invasion and expression levels of PI3K, phosphorylated (p-) PI3K, AKT and p-AKT were determined using Cell Counting Kit-8, TUNEL, Transwell assays and western blotting. Moreover, ITGA7 in tumor and adjacent tissues from 50 patients with endometrial cancer was detected using immunohistochemical assay. ITGA7 expression was increased in EC cell lines (HEC-1A, RL95-2, Ishikawa and KLE) compared with telomerase-immortalized human endometrial stromal cells (THESCs). In both Ishikawa and RL95-2 cells, three ITGA7 siRNAs all demonstrated good efficiency on ITGA7 knockdown, amongst which the one with the highest efficiency was selected for the following experiments. ITGA7 knockdown reduced cell proliferation and invasion, while inducing apoptosis; moreover, it suppressed p-PI3K/PI3K and p-AKT/AKT ratios. In patients with EC, ITGA7 expression was increased in tumor tissues compared with adjacent tissues, and its lower tumor expression was associated with myometrial invasion (<1/2), non-lymphovascular invasion and decreased FIGO stage. In conclusion, ITGA7 knockdown repressed proliferation, invasion and the PI3K/AKT pathway while inducing apoptosis in EC cell lines, and its insufficiency was associated with less advanced tumor features in EC patients. These results indicated that ITGA7 may be a potential target for the treatment of EC.

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Suppression of synuclein gamma inhibits the movability of endometrial carcinoma cells by PI3K/AKT/ERK signaling pathway

Cited by 6 publications

References 30 publications

Subvacuum environment‐enhanced cell migration promotes wound healing without increasing hypertrophic scars caused by excessive cell proliferation

Subvacuum environment‐enhanced cell migration promotes wound healing without increasing hypertrophic scars caused by excessive cell proliferation

The Herbal Combination Shu Gan Jie Yu Regulates the SNCG/ER-a/AKT-ERK Pathway in DMBA-Induced Breast Cancer and Breast Cancer Cell Lines Based on RNA-Seq and IPA Analysis

Effect of integrin α7 on cell proliferation, invasion, apoptosis and the PI3K/AKT pathway, and its association with clinicopathological features in endometrial cancer

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