Erbin inhibits TGF-β1-induced EMT in renal tubular epithelial cells through an ERK-dependent pathway

Zhou, Qin; Zeng, Rui; Xu, Chuou; Liu, Huan; Chen, Lin; Kou, Pei; Pei, Guangchang; Bai, Shoujun; Zhang, Yamin; Li, Caixia; Rong, Song; Han, Min; Xu, Gang

doi:10.1007/s00109-011-0833-4

Cited by 28 publications

(24 citation statements)

References 32 publications

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“…The MAPK pathway is a highly conserved pathway involved in diverse cellular functions, including cell proliferation, cell differentiation and apoptosis, while JNK, p38 MAPK and ERK in this pathway are involved in a Zn-sensing process [32, 33]. The results from the present study indicated that over-expression ZnT7 significantly inhibited HG-induced expression of phospho-ERK but not phospho-p38 MAPK.…”

Section: Discussionsupporting

confidence: 66%

Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Zhang

Liang³

et al. 2018

Kidney Blood Press Res

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Background/Aims: Evidence from our and other groups has demonstrated that zinc transporter 7 in SLC30 family (ZnT7) inhibited epithelial-to-mesenchymal transition (EMT) and apoptosis in rat peritoneal mesothelial cells (RPMCs) under high glucose (HG) concentration. In the present study, we investigated the effect of ZnT7 on EMT of renal tubular epithelial cells (RTECs) in an in vitro model of diabetic nephropathy (DN). Methods: A dual-fluorescent staining protocol was used for detection of ZnT7 in a normal rat kidney tubular epithelial cell line (NRK-52E cells). EMT was induced with HG (30 mM). NRK-52E cells were transfected with plasmids codifying for hZnT7-EGFP and interfering RNA for determination of the effect of ZnT7 over-expression and silencing, respectively. Expression of ZnT7, activation of the MAPK/ERK and TGF-β/Smad pathways were analyzed with by means of Western blot. Results: ZnT7 was localized in the perinuclear region and Golgi apparatus. In HG-induced EMT of NRK-52E cells, ZnT7 was up-regulated. Over-expression of ZnT7 led to inhibition of HG-induced EMT, while knock-down of ZnT7 increased EMT. Furthermore, knock-down of ZnT7 and increased HG-induced EMT was accompanied by activation of the MAPK/ERK and TGF-β/Smad pathways. Conclusion: The present study provides evidence that ZnT7 has a protective effect over EMT of RTECs in DN and suggests that the inhibition of HG-induced EMT may be achieved through the MAPK/ERK and TGF-β/Smad pathways. Thereby, ZnT7 could be a potential target for translation medicine and prevention program in DN.

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Section: Discussionsupporting

confidence: 66%

Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Zhang

Liang³

et al. 2018

Kidney Blood Press Res

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“…These results all indicate that ACY1 functions via the ERK pathway. Furthermore, activation of ERK increases the expression of TGF-β, another important factor involved in tumor progress (13,(15)(16)(17), and TGF-β could therefore directly attenuate the immune system and promote tumor proliferation (13,17). Thus, decreased expression of TGF-β could lead to tumor inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…As predicted, this revealed that silencing of ACY1 reduced the level of ERK1 expression in colorectal cancer tissue, which indicates that there is an overexpression of ERK1 along with ACY1 in colorectal cancer. In addition, since it is well known that activation of ERK leads to increased TGF-β1 expression (13,15,16), the association between ACY1 and TGF-β1 expression was measured, which revealed a positive association between the two. The results of the present study indicate that the ERK and TGF-β1 function downstream of ACY1 and facilitate the tumor-promoting effect of ACY1.…”

Section: Discussionmentioning

confidence: 99%

“…In small cell lung cancer (SCLC), renal cell carcinoma and liver cancer ACY1 expression has been demonstrated to be significantly reduced (10)(11)(12)(13), suggesting that ACY1 serves a role in inhibiting tumorigenesis. Limited studies have investigated the detailed function and mechanism of ACY1 in tumor proliferation, and certain previous studies have reported that activation of ERK 1/2 and expression of TGF-β may be implicated in this process (13)(14)(15)(16). However, the role of ACY1 in gastrointestinal cancer remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Study of the expression and function of ACY1 in patients with colorectal cancer

Liu

Cao

et al. 2017

Oncology Letters

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Abstract. Aminoacylase 1 (ACY1) is important for regulating the proliferation of numerous types of cancer. However, the expression and mechanisms underlying the function of ACY1 in colorectal cancer remain unclear. In order to investigate the expression and function of ACY1 in colorectal cancer, tumor tissue and blood samples were collected for analysis from 132 patients diagnosed with colorectal cancer. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting identified significantly increased expression of ACY1 mRNA in colorectal tumor tissue (P<0.05 vs. adjacent normal tissue) and notably increased ACY1 protein levels. This ACY1 mRNA expression was found to be positively correlated with tumor stage. In addition, plasma ACY1 concentration was increased in patients with colorectal cancer compared with healthy controls. Furthermore, in vitro knockdown of ACY1 in human colorectal cancer HT-29 cells was shown to inhibit proliferation and increase apoptosis. This effect was found to be associated with the activation of ERK1 and TGF-β1 signaling. In conclusion, the results of the present study suggest that ACY1 promotes tumor progression, and thus may be a potential target for the diagnosis and treatment of colorectal cancer. IntroductionColorectal cancer, the third most common cancer worldwide, is a major public health issue in China and globally (1). Although advances have been made in surgical and medical treatments, ~40% of patients with colorectal cancer succumb to the cancer (2). The early diagnosis and assessment of tumors is an area of intense study; however, it is a complex issue. Previous studies indicate that tumor cells of different clinical stages may exhibit different expression levels of certain biomarkers, which could be used as a target for the diagnosis or treatment of the tumor (3-5). In addition, with ongoing and advancing research into tumor biology, new targets are being identified and studied, including aminoacylase 1 (ACY1) (6).ACY1 is a cytosolic enzyme that deacylates the α-acylated amino acid from the N-terminal peptide of intracellular proteins (6). Following this, terminal acetylated proteins are more stable (7-9). In addition to its function in scavenging N-acylated amino acids, ACY1 has been studied in a number of types of human cancer. In small cell lung cancer (SCLC), renal cell carcinoma and liver cancer ACY1 expression has been demonstrated to be significantly reduced (10-13), suggesting that ACY1 serves a role in inhibiting tumorigenesis. Limited studies have investigated the detailed function and mechanism of ACY1 in tumor proliferation, and certain previous studies have reported that activation of ERK 1/2 and expression of TGF-β may be implicated in this process (13-16). However, the role of ACY1 in gastrointestinal cancer remains unclear. In the present study, the function and regulation of ACY1 in colorectal cancer was investigated through analyzing clinical samples. Materials and methodsPatients and clinical specimens. In total, 160 patients ...

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“…Preventing EMT-associated signaling pathways plays an important role in inhibiting cancer cell migration and invasion, as well as reducing drug resistance (12). The occurrence of the EMT is associated with complex signaling pathways, including the Wnt, PI3K, Hedgehog, transforming growth factor-β (TGF-β) and Notch pathways (16)(17)(18). However, the details of these mechanisms in HCT-8 colon cancer cells are yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Acquisition of 5-fluorouracil resistance induces epithelial-mesenchymal transitions through the Hedgehog signaling pathway in HCT-8 colon cancer cells

Liu

Zhao

et al. 2015

Oncology Letters

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Abstract. Colon cancer has a high incidence in individuals >60-years-old. The commonly used chemotherapeutic agent, 5-fluorouracil (5-FU), has gradually lost its potency in treating colorectal cancer following the acquisition of resistance. Drug resistance is usually associated with epithelial-mesenchymal transitions (EMTs) in cancer cells. In the present study, the EMT phenotypes of two colon cancer cell lines, wild-type (HCT-8/WT) and 5-FU-resistant (HCT-8/5-FU), were characterized following the analysis of cellular migration, proliferation, morphology and molecular changes. In order to further clarify the mechanism of EMT in HCT-8/5-FU cells, the effect of EMT pathway inhibitors upon drug sensitivity was investigated. The results revealed that the Hedgehog signaling pathway inhibitor, GDC0449, reversed drug resistance. Therefore, inhibition of the Hedgehog pathway may provide a novel chemotherapeutic strategy for the treatment of patients with 5-FU-resistant colon cancer.

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Erbin inhibits TGF-β1-induced EMT in renal tubular epithelial cells through an ERK-dependent pathway

Cited by 28 publications

References 32 publications

Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Protective Effect of Znt7 on High Glucose-Induced Epithelial-to-Mesenchymal Transition in Renal Tubular Epithelial Cells

Study of the expression and function of ACY1 in patients with colorectal cancer

Acquisition of 5-fluorouracil resistance induces epithelial-mesenchymal transitions through the Hedgehog signaling pathway in HCT-8 colon cancer cells

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