A Soft Microenvironment Protects from Failure of Midbody Abscission and Multinucleation Downstream of the EMT-Promoting Transcription Factor Snail

Simi, Allison K.; Anlaş, Alişya A.; Stallings-Mann, Melody; Zhang, Sherry; Hsia, Tiffaney; Cichon, Magdalena A.; Radisky, Derek C.; Nelson, Celeste M.

doi:10.1158/0008-5472.can-17-2899

Cited by 30 publications

(42 citation statements)

References 57 publications

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“…These results demonstrated that snail is involved in the EMT process of human renal tubular epithelial cells [30]. The promotion of EMT in renal tubular epithelial cells by snail is regulated by many upstream signaling pathways, and Notch signaling pathway is one of them [9]. It was shown that activation of Notch2 and Notch4 promotes the activation of Snail.…”

Section: Discussionmentioning

confidence: 77%

“…The expression of snail is regulated by a variety of signaling pathways, including Notch signaling pathway. Recent studies have shown that induction of EMT by Notch signaling pathway in renal tissue requires activation of snail molecule, and the expression of Snail1 is directly regulated by Notch signaling [9]. Thus, Notch / Snail pathway is an important pathological mechanism of renal interstitial fibrosis in DN and may be a potential therapeutic target for interstitial fibrosis.…”

Section: Introductionmentioning

confidence: 99%

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Gliquidone Alleviates Diabetic Nephropathy by Inhibiting Notch/Snail Signaling Pathway

Tian

Yang

Xie

et al. 2018

Cell Physiol Biochem

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Background/Aims: Diabetic nephropathy is a common complication of diabetes. This study explored the renal protective effect and possible mechanism of gliquidone in mice with diabetic nephropathy. Methods: Animal model of diabetic nephropathy was established in KKAy mice. The renal protective effect of gliquidone was studied by evaluating the kidney function through measures of urinary protein, blood urea nitrogen (BUN), serum creatinine (Scr) and serum triglyceride (TG) that were performed using an automatic biochemical analyzer. The levels of oxidative stress indicators, such as nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA), were evaluated in renal tissue homogenates using the automatic biochemical analyzer. The inhibitory effect of gliquidone on renal interstitial fibrosis and its association with Notch / Snail1 signaling pathway in diabetic nephropathy was investigated using molecular biological techniques. Results: It was found that low-, medium- and high-dose gliquidone improved the mice’s general health condition, such as mental status, fur condition, eating, and drinking. Gliquidone reduced the body weight and the kidney weight /body weight ratio of mice. Gliquidone improved the kidney function, indicated by reductions in urinary protein, blood urea nitrogen, and serum creatinine and triglyceride. Gliquidone treatment increased levels of nitric oxide and superoxide dismutase, but decreased level of malondialdehyde. The expression of Jagged1/Notch1/hes1/Snail1/α-SMA decreased, while the expression of E-cadherin increased in gliquidone-treated kidneys. High dose gliquidone showed the best effect, one that was similar to that of the positive control drug irbesartan. Conclusion: Taken together, our results suggested that gliquidone can ameliorate the diabetic symptoms of diabetic nephropathy through inhibiting Notch / Snail1 signaling pathway, improving anti -oxidative response and delaying renal interstitial fibrosis. The efficacy of gliquidone is dose-dependent.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Gliquidone Alleviates Diabetic Nephropathy by Inhibiting Notch/Snail Signaling Pathway

Tian

Yang

Xie

et al. 2018

Cell Physiol Biochem

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“…Although septins neither present motor activity, nor force generation, due to their interactions with the mechanotransduction machinery, they are supposed to have a role in mechanobiology and in the regulation of mechanotransductional pathways (Calvo et al 2015;Dolat et al 2014a, b;Simi et al 2018). Potentially affecting the conformation of stretch-sensitive ion channels, they might be able to modify the stretch-activated cellular responses and downstream mechanotransduction (Pardo-Pastor et al 2018;Coste et al 2010).…”

Section: Cellular Function Of Septin Proteinsmentioning

confidence: 99%

Septins, a cytoskeletal protein family, with emerging role in striated muscle

Gönczi

Dienes

Dobrosi

et al. 2020

J Muscle Res Cell Motil

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Appropriate organization of cytoskeletal components are required for normal distribution and intracellular localization of different ion channels and proteins involved in calcium homeostasis, signal transduction, and contractile function of striated muscle. Proteins of the contractile system are in direct or indirect connection with the extrasarcomeric cytoskeleton. A number of other molecules which have essential role in regulating stretch-, voltage-, and chemical signal transduction from the surface into the cytoplasm or other intracellular compartments are already well characterized. Sarcomere, the basic contractile unit, is comprised of a precisely organized system of thin (actin), and thick (myosin) filaments. Intermediate filaments connect the sarcomeres and other organelles (mitochondria and nucleus), and are responsible for the cellular integrity. Interacting proteins have a very diverse function in coupling of the intracellular assembly components and regulating the normal physiological function. Despite the more and more intense investigations of a new cytoskeletal protein family, the septins, only limited information is available regarding their expression and role in striated, especially in skeletal muscles. In this review we collected basic and specified knowledge regarding this protein group and emphasize the importance of this emerging field in skeletal muscle biology.

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“…With the increase concentration of BBR and MET, the number of gastric cancer cells that invaded and metastasized gradually decreased. Matrix metalloproteinase-3 (MMP-3), known as inducers of EMT, is one of the several MMPs that regulate angiogenesis, invasion and metastasis ( Huang et al, 2016 ; Chu et al, 2018 ; Simi et al, 2018 ). It was reported that MMP-3 expression level was negatively correlated with GC development ( Xu et al, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

“…With the increased dose of BBR, the number of gastric cancer cells that invaded and metastasized dramatically decreased. MMP-3, known as inducers of EMT, is one of the several MMPs that regulate angiogenesis, invasion and metastasis ( Huang et al, 2016 ; Chu et al, 2018 ; Simi et al, 2018 ).It was reported that MMP-3 expression level was negatively correlated with GC development ( Xu et al, 2016 ). We also found that BBR had stable inhibitory effect on matrix metalloproteinase-3 (MMP-3) protein and mRNA expressions in AGS and SGC7901 cells, which suggested that BBR inhibited the migration and invasion to prevent GC development through downregulating MMP-3 in AGS and SGC7901 GC cells.…”

Section: Discussionmentioning

confidence: 99%

Berberine Attenuated Proliferation, Invasion and Migration by Targeting the AMPK/HNF4α/WNT5A Pathway in Gastric Carcinoma

Zou

et al. 2018

Front. Pharmacol.

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Background: Recent epidemiologic studies have found that patients with diabetes have a higher risk of gastric cancer (GC), and the long-term use of metformin is associated with a lower risk of gastric cancer. It is believed that blocking tumor energy metabolic alterations is now emerging as a new therapeutic approach of cancer. Berberine, a natural isoquinoline alkaloid, could modulate lipid metabolism and glucose homeostasis by regulating the expression of HNF4α in many metabolic diseases. Here, we investigated the effect of Berberine on GC and its possible molecular mechanism through targeting HNF4α.Methods and Results: (1) AGS and SGC7901 gastric cancer cells were treated with Berberine (BBR). We found that in AGS and SGC7901 cell, BBR inhibited cell proliferation in a time- and dose-dependent manner through downregulating C-myc. BBR also induced G0-G1 phase arrest with the decreased expression of cyclin D1. Moreover, BBR attenuated the migration and invasion by downregulating MMP-3. (2) The lentivirus infection was used to silence the expression of HNF4α in SGC7901 cell. The results demonstrated that the knockdown of HNF4α in SGC7901 slowed cells proliferation, induced S phase arrest and dramatically attenuated gastric cancer cells’ metastasis and invasion. (3) We performed GC cells perturbation experiments through BI6015 (an HNF4α antagonist), AICAR (an AMPK activator), Compound C (AMPK-kinase inhibitor), metformin and BBR. Our findings indicated that BBR downregulated HNF4α while upregulating p-AMPK. Moreover, the inhibition of HNF4α by BBR was AMPK dependent. (4) Then the LV-HNF4α-RNAi SGC7901 cell model was used to detect the downstream of HNF4α in vitro. The results showed that the knockdown of HNF4α significantly decreased WNT5A and cytoplasmic β-catenin, but increased E-cadherin in vitro. Berberine also downregulated WNT5A and cytoplasmic β-catenin, the same as LV-HNF4α-RNAi and BI6015 in GC cells. (5) Finally, the SGC7901 and LV-HNF4α-RNAi SGC7901 mouse-xenograft model to evaluate the effect of BBR and HNF4α gene on GC tumor growth. The result illustrated that BBR and knockdown of HNF4α suppressed tumor growth in vivo, and BBR decreased HNF4α, WNT5A and cytoplasmic β-catenin levels, the same effect as HNF4α knockout in vivo.Conclusion: BBR not only had proliferation inhibition effect, attenuated the invasion and migration on GC cell lines, but also suppressed the GC tumor growth in vivo. The anti-gastric cancer mechanism of BBR might be involved in AMPK-HNF4α-WNT5A signaling pathway. HNF4α antagonists, such as BBR, could be a promising anti-gastric cancer treatment supplement.

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A Soft Microenvironment Protects from Failure of Midbody Abscission and Multinucleation Downstream of the EMT-Promoting Transcription Factor Snail

Cited by 30 publications

References 57 publications

Gliquidone Alleviates Diabetic Nephropathy by Inhibiting Notch/Snail Signaling Pathway

Gliquidone Alleviates Diabetic Nephropathy by Inhibiting Notch/Snail Signaling Pathway

Septins, a cytoskeletal protein family, with emerging role in striated muscle

Berberine Attenuated Proliferation, Invasion and Migration by Targeting the AMPK/HNF4α/WNT5A Pathway in Gastric Carcinoma

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