The role of TGF-β-related signal transduction pathways in pathogenesis of epithelial-mesenchymal transition as a key element in cancer development and progression

Pieniążek, Małgorzata; Donizy, Piotr; Ziętek, Marcin; Szynglarewicz, B.; Matkowski, Rafał

doi:10.5604/17322693.1009653

Cited by 14 publications

(9 citation statements)

References 89 publications

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“…SMAD1 belongs to the BMP superfamily of ligands and is involved in complex cell signaling [ 14 – 18 ]. We further explored the pathway by which miR-26b-5p and SMAD1 exert their functions in HCC.…”

Section: Discussionmentioning

confidence: 99%

Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma

et al. 2016

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Twist1 is well known to induce epithelial-mesenchymal transition (EMT) and promote tumor metastasis. MicroRNAs (miRNAs) are involved in the EMT process and are associated with metastasis in hepatocellular carcinoma (HCC). In the present study, microRNA-26b-5p (miR-26b-5p) expression was consistently and significantly downregulated in HepG2-Twist1 HCC cell lines compared with HepG2-vector cell lines using microarrays (the HepG2-Twist1 cell line can stably express Twist1). miR-26b- 5p downregulation was directly mediated by Twist1 through binding to the promoter region of miR-26b-5p in HepG2-Twist1 cells by ChIP-seq technology. Both gain- and loss-of-function studies showed that miR-26b-5p dramatically suppressed EMT and the invasion ability of HCC cells in vitro. Using mouse models, tumors derived from miR- 26b-5p-overexpressed HCC cells exhibited a significant reduction in tumorigenicity compared with the control group. Subsequent investigation revealed that miR-26b-5p directly inhibited SMAD family member 1 (SMAD1) expression. miR-26b-5p repressed BMP4/Smad1 signaling following SMAD1 inhibition. Overexpression of SMAD1 reversed the function of miR-26b-5p. In human HCC tissues and mouse xenograft tumors, miR-26b-5p levels were inversely correlated with SMAD1 expression as well as metastasis. Conclusion: miR-26b-5p suppresses Twist1-induced EMT, invasion, and metastasis of HCC cells by targeting SMAD1 and BMP4/Smad1 signaling. This suggests a promising application for miR-26b-5p in anti-HCC therapy.

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Section: Discussionmentioning

confidence: 99%

Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma

et al. 2016

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“…Among them, TGF-β is the most thoroughly studied and commonly used EMT inducible factor. 18 GRHL2 has been studied in other tumors such as breast cancer in the past, the innovation of our research is slightly inadequate. But we knocked down or overexpressed GRHL2 in three CRC cell lines, sufficiently demonstrated the effect of GRHL2 on EMT in colorectal cancer, which had a certain value.…”

Section: Discussionmentioning

confidence: 99%

GRHL2 inhibits colorectal cancer progression and metastasis via oppressing epithelial-mesenchymal transition

Zhou

Chen

et al. 2019

Cancer Biology & Therapy

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Our previous study has demonstrated that knockdown of Grainyhead-like 2(GRHL2) in colorectal cancer (CRC) cells inhibited cell proliferation by targeting ZEB1. This study aimed at researching whether knockdown of GRHL2 promoted CRC progression and metastasis via inducing epithelial-mesenchymal transition (EMT). GRHL2-upregulated SW-620/GRHL2+ and GRHL2-knockdown HCT116/GRHL2-KD, HT29/ GRHL2-KD cells and their control cells were generated. The morphological changes after overexpression and knockdown GRHL2 were observed. qRT-PCR, Western blotting, and Immunofluorescence were used to detect EMT markers: E-cadherin, Vimentin, p-catein, ZO-1 and ZEB1 expression. Then, sh-ZEB1 was transfected to GRHL2 knockdown cells to research the relationship between GRHL2 and ZEB1. Transwell and wound healing assays were further performed to detect the impact of GRHL2 on invasion and migration in vitro. CRC cells were injected into mice tail vein to verify the impact of GRHL2 on CRC metastasis. Morphological change of mesenchymal-epithelial transition (MET) could be observed in SW620/GRHL2+ cell. The expression of epithelial markers: E-cadherin, β-catenin, ZO-1 were upregulated, while mesenchymal markers: Vimentin was decreased. Meanwhile, opposite EMT morphological change could be observed in HCT116/GRHL2-KD cell, accompanied by reverse change of E-cadherin, β-catenin, ZO-1, and Vimentin. The expression level of GRHL2 and ZEB1 was found negative in both SW620/GRHL2+ and HCT116/GRHL2-KD cells. Knockdown of ZEB1 by siRNA in HCT116/GRHL2-KD and HT29/GRHL2-KD could upregulate expression of E-cadherin and GRHL2. GRHL2 knockdown also promoted migration, invasion in vitro and CRC metastasis in mice model. In conclusion, GRHL2/ZEB1 axis inhibits CRC progression and metastasis via oppressing EMT.

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“…Extinction of the inflammatory reaction results in termination of the EMT and a return to the original state. Long-term support of the EMT process leads to fibrous degeneration as well as structural and functional tissue and organ disorders [31,32]. Pleiotropic TGF-β molecules and bone morphogenetic proteins (BMPs), belonging to the transforming growth factor-β (TGF-βSF) superfamily, participate in one of the most well-known signalling pathways in the ETM process [33–35].…”

Section: Discussionmentioning

confidence: 99%

Urinary proteome of dogs with kidney injury during babesiosis

Winiarczyk

Michalak

Adaszek

et al. 2019

Preprint

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This study aimed to identify proteins found in the urine of dogs with renal dysfunction leading to acute injury during the natural course of babesiosis (n=10) and to compare them with proteins of a control group (n=10) to reveal any potential biomarkers of renal damage. Pooled urine samples of both groups were separated by 2D electrophoresis (two dimensional electrophoresis), followed by the identification of all proteins using MALDI-TOF mass spectrometry (matrix assisted laser desorption ionization-time of flight). In total, 176 proteins were identified in the urine samples from healthy dogs, and 403 proteins were identified in the urine samples from dogs with babesiosis. Of the 176 proteins, 146 were assigned exclusively to healthy dogs, and 373 of the 403 proteins were assigned exclusively to dogs with babesiosis; 30 proteins were common to both groups. Characteristic analysis of the 373 proteins found in dogs with babesiosis led to the isolation of 8 proteins associated with 10 metabolic pathways that were attributed to immune and inflammatory response development. Furthermore, it was hypothesized that the epithelial-mesenchymal transition might play an important role in mechanisms underlying pathological renal tissue changes during babesiosis, as indicated by a causal relationship network built by combining 5 of the 10 selected metabolic pathways and 4 of the 8 proteins associated with these pathways. These included cadherins, gonadotropin releasing hormone receptors, inflammatory responses mediated by chemokine and cytokine signalling pathways, integrins, interleukin and TGF-β (transforming growth factor β) pathways. These pathways were linked by interleukin-13, bone morphogenetic protein 7, α2(1) collagen, and FER tyrosine kinase, which are potential damage biomarkers during babesiosis in dogs that might be assigned to early renal injury. Keywords: Acute kidney injury; Babesiosis; Dog; Proteomics; Urine

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The role of TGF-β-related signal transduction pathways in pathogenesis of epithelial-mesenchymal transition as a key element in cancer development and progression

Cited by 14 publications

References 89 publications

Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma

Twist1-related miR-26b-5p suppresses epithelial-mesenchymal transition, migration and invasion by targeting SMAD1 in hepatocellular carcinoma

GRHL2 inhibits colorectal cancer progression and metastasis via oppressing epithelial-mesenchymal transition

Urinary proteome of dogs with kidney injury during babesiosis

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