Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

Wang, Lishan; Bai, Ying; Yang, Yang; Hu, Fangfang; Yong-hui, Wang; Yu, Zhenxin; Cheng, Zhao; Zhou, Jiahua

doi:10.18632/oncotarget.9533

Cited by 31 publications

(34 citation statements)

References 26 publications

(25 reference statements)

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“…P38 MAPK is one of the important members of MAPK [52, 53]. Acting as an integration point for multiple biochemical signals, MAPK participates in a wide variety of cellular processes such as proliferation, differentiation and apoptosis [54-56]. The p38 MAPK pathway is known to play an important role in podocyte apoptosis [33, 57].…”

Section: Discussionmentioning

confidence: 99%

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Podocyte injury, especially podocyte apoptosis, plays a major role in early-stage diabetic nephropathy (DN). Swiprosin-1, also known as EF hand domain containing 2 (EFhd2), is a Ca²⁺-binding protein in different cell types. However, the function of swiprosin-1 in podocytes remains unknown. Methods: The expression and distribution of swiprosin-1 were investigated in the mouse renal glomerulus and conditionally immortalized mouse podocyte cell line MPC-5. The expression of swiprosin-1 was also detected in streptozotocin (STZ)-treated mice and MPC-5 cells treated with high glucose (HG). Nephrin and podocin were detected by immunohistochemistry and immunofluroscence. Collagen IV, transforming growth factor-β (TGF-β) and fibronectin mRNA expressions were assayed by real-time PCR. Apoptotic proteins and phosphorylation of p38 mitogen-activated protein kinase (MAPK) were detected by immunoblotting. Results: Swiprosin-1 was found to be expressed in podocytes of the mouse glomerulus and MPC-5 cells. Swiprosin-1 expression was increased in STZ-treated mice and MPC-5 cells treated with HG. In Swiprosin-1-/- diabetic mice, kidney/ body weight, urinary albumin, podocyte foot process effacement and glomerular basement membrane thickening were attenuated; the downregulation of nephrin and podocin expression in the glomerulus was inhibited; and the upregulation of collagen IV, TGF-β and fibronectin mRNA expression in the renal cortex was ameliorated as compared with those in diabetic swiprosin-1+/+ mice. In addition, the increased apoptosis of podocytes, proapoptotic protein expression and p38 phosphorylation in Swiprosin-1-/- diabetic mice were inhibited as compared with those in diabetic swiprosin-1+/+ mice. Knockdown of swiprosin-1 in MPC-5 cells reduced the apoptosis of podocytes, proapoptotic protein expression and p38 phosphorylation induced by HG. Targeted knockdown of p38 attenuated the increased apoptosis of MPC-5 cells over-expressing swiprosin-1. Conclusion: Swiprosin-1 expression in podocytes of the mouse glomerulus played a critical role in early-stage DN. Swiprosin-1 deficiency in early DN attenuated mitochondria-dependent podocyte apoptosis induced by hyperglycemia or HG via p38 MAPK signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

Wang

et al. 2018

Cell Physiol Biochem

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“…[23] Diabetes mellitus stimulates pancreatic cancer growth via the MAPK pathway. [24] High glucose increases glucose uptake and glycolytic activity, and stimulates cell proliferation through modulating the MAPK pathway. [25] Apart from PI3K/Akt pathway, MAPK pathway should be suspected to activate and greatly implicate in PTC development.…”

Section: Discussionmentioning

confidence: 99%

Expression characteristics of proteins of IGF-1R, p-Akt, and survivin in papillary thyroid carcinoma patients with type 2 diabetes mellitus

Yan

Hu²,

Wu³

et al. 2017

Medicine

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Type 2 diabetes mellitus (T2DM) is related to increased risk of papillary thyroid carcinoma (PTC). Insulin-like growth factor-1 receptor (IGF-1R) is increased in patients with T2DM. The increased IGF-1R may be responsible for the development of PTC. In this study, we investigated the expression of phosphorylation of Akt (p-Akt)/survivin pathway activated by IGF-1R in PTC subjects with and without diabetes.Clinicopathological data of 20 PTC patients with T2DM were retrospectively analyzed and compared with those of 21 PTC subjects without diabetes. Meanwhile, IGF-1R, p-Akt, and survivin expressions of PTC tissues were detected by immunohistochemical staining.The immunohistochemical results found that the expression level of IGF-1R was significantly higher in diabetic PTC patients than that in nondiabetic PTC patients (P < 0.05). However, no significant differences of p-Akt and survivin expression were found between PTC patients with T2DM and PTC patients without T2DM. In addition, among 20 PTC patients with T2DM, subgroup analysis showed that the ratio of tumor size >10 mm was significantly higher in IGF-1R moderate to strong expression group than that in IGF-1R negative to weak expression group (P < 0.05).IGF-1R expression level was higher in PTC patients with T2DM, and the increased IGF-1R expression was associated with lager tumor size. IGF-1R may play an important role in carcinogenesis and tumor growth in PTC patients with T2DM.

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“…Once activated, p38 MAPKs phosphorylate the serine/threonine residues of their substrates, which include several transcription factors as well as protein kinases (38). It has been reported that the activation and phosphorylation of p38 MAPK mediates the anticancer activity in numerous malignant cancers such as pancreatic (39) and gastric cancer (40), and head and neck carcinoma (41).…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine inhibits the proliferation of human osteosarcoma cells by upregulating the PTEN pathway

Tian

Zhang

et al. 2017

Oncology Reports

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Tetrandrine (TET) is a natural product isolated from the Chinese herb Stephania tetrandra S. Moore and has been reported to have antiproliferation and apoptosis-inducing activity in various malignant tumor cells. However, the exact molecular mechanisms underlying these effects remain unclear. In the present study, we tested the antiproliferation effect of TET on osteosarcoma (OS) 143B cells and explored the possible potential molecular mechanism in this process. Using CCK-8 assay and flow cytometry, we found that TET inhibited proliferation, induced apoptosis and arrested the cell cycle of the 143B cells. Using a xenograft tumor model of human OS, tetrandrine was found to inhibit tumor growth in vivo. TET increased the protein level of phosphatase and tensin homolog (PTEN) and decreased its phosphorylation as detected by western blot analysis and immunohistochemistry.Overexpression of PTEN strengthened the anticancer effect of TET, while knockdown of PTEN attenuated it. Meanwhile, TET activated p38 MAPK and increased its phosphorylation. Our findings suggest that TET may be a potential anticancer drug for OS. In addition, its effects may be mediated by the upregulation of PTEN. Moreover the expression alteration of PTEN and p-PTEN was mediated by the TET-induced activation of p38 MAPK in a direct or indirect manner.

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Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

Cited by 31 publications

References 26 publications

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

Swiprosin-1 Promotes Mitochondria-Dependent Apoptosis of Glomerular Podocytes via P38 MAPK Pathway in Early-Stage Diabetic Nephropathy

Expression characteristics of proteins of IGF-1R, p-Akt, and survivin in papillary thyroid carcinoma patients with type 2 diabetes mellitus

Tetrandrine inhibits the proliferation of human osteosarcoma cells by upregulating the PTEN pathway

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