TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway

Zhu, Linan; Zhang, Xudong; Fu, Xiaorui; Li, Zhaoming; Sun, Zhenchang; Wu, Jingjing; Wang, Xinhua; Wang, Feng; Li, Xiangke; Niu, Songtao; Ding, Mengjie; Yang, Zhenzhen; Yang, Wanqiu; Yin, Meifeng; Zhang, Lei; Zhang, Mingzhi

doi:10.1186/s12967-018-1383-0

Cited by 20 publications

(21 citation statements)

References 35 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The assay was performed by using a Cell-Light™ EdU Apollo 567 In Vitro Imaging Kit (EdU; Guangzhou RiboBio, Guangzhou, China) as described previously [37]. Briefly, 5000 pMSCs were plated into 96-well tissue culture plates for 48 h, and the cells were exposed to EdU at a concentration of 50 μM and incubated for 2 h, followed by fixation with 4% formaldehyde for 30 min.…”

Section: Methodsmentioning

confidence: 99%

TZAP plays an inhibitory role in the self-renewal of porcine mesenchymal stromal cells and is implicated the regulation of premature senescence via the p53 pathway

Bie

Chen

et al. 2019

J Transl Med

View full text Add to dashboard Cite

Background Mesenchymal stromal cells (MSCs) were originally characterized by the ability to differentiate into different mesenchymal lineages in vitro, and their immunomodulatory and trophic functions have recently aroused significant interest in the application of MSCs in cell-based regenerative medicine. However, a major problem in clinical practice is the replicative senescence of MSCs, which limits the cell proliferation potential of MSCs after large-scale expansion. Telomeric zinc finger-associated protein (TZAP), a novel specific telomere-binding protein, was recently found to stimulate telomere trimming and prevent excessive telomere elongation. The aim of this study was to elucidate the role of TZAP in regulating MSCs senescence, differentiation and proliferation. Method Primary porcine mesenchymal stromal cells (pMSCs) were isolated from the bone marrow of Tibet minipigs by a noninvasive method in combination with frequent medium changes (FMCs). The deterioration of the pMSCs’ proliferation capacity and their resultant entry into senescence were analyzed by using CCK8 and EdU incorporation assays, SA-β-gal staining and comparisons of the expression levels of cellular senescence markers (p16INK14 and p21) in pMSC cell lines with TZAP overexpression or knockout. The effects of TZAP overexpression or knockout on the differentiation potential of pMSCs were assessed by alizarin red S staining after osteogenic induction or by oil red O staining after adipogenic induction. The effect of TZAP overexpression and the involvement of the p53 signaling pathway were evaluated by detecting changes in ARF, MDM2, P53 and P21 protein levels in pMSCs. Results TZAP levels were significantly elevated in late-passage pMSCs compared to those in early-passage pMSCs. We also observed significantly increased levels of the senescence markers p16INK4A and p21. Overexpression of TZAP reduced the differentiation potential of the cells, leading to premature senescence in early-passage pMSCs, while knockout of TZAP led to the opposite phenotype in late-passage pMSCs. Furthermore, overexpression of TZAP activated the P53 pathway (ARF-MDM2-P53-P21WAF/CDKN1A) in vitro. TZAP also downregulated the expression levels of PPARγ and Cebpα, two key modulators of adipogenesis. Conclusions This study demonstrates that the level of TZAP is closely related to differentiation potential in pMSCs and affects cellular senescence outcomes via the p53 pathway. Therefore, attenuation of intracellular TZAP levels could be a new strategy for improving the efficiency of pMSCs in cell therapy and tissue engineering applications. Electronic supplementary material The online version of this article (10.1186/s12967-019-1820-8) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

TZAP plays an inhibitory role in the self-renewal of porcine mesenchymal stromal cells and is implicated the regulation of premature senescence via the p53 pathway

Bie

Chen

et al. 2019

J Transl Med

View full text Add to dashboard Cite

show abstract

“…PEDF is a 50 kDa secreted protein which is a versatile member of the widely expressed serpin family, also denoted as SERPINF1 (1). It plays important roles in angiogenesis, fibrogenesis, neuroprotection, bone matrix mineralization, and inflammation (4).…”

Section: Discussionmentioning

confidence: 99%

“…Esophageal carcinoma is a common gastrointestinal cancer that has two major subtypes: adenocarcinoma and squamous cell carcinoma (1). It is the sixth cancer-related deaths worldwide.…”

Section: Introductionmentioning

confidence: 99%

“…There are ∼5,500 confirmed cases of disease in 5 million people each year in Huai'an city, the northern part of Jiangsu Province, China. Although progress has been made in the diagnosis and treatment of esophageal carcinoma, its 5-year survival rate is still dismal (1). Therefore, it is imperative to further explore the molecular basis of esophageal carcinoma and develop more effective treatment strategy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pigment Epithelium-Derived Factor Promotes the Growth and Migration of Human Esophageal Squamous Cell Carcinoma

Tang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Pigment epithelium-derived factor (PEDF) is an oncogene found in various types of cancers. However, how PEDF affects the development of human esophageal squamous cell carcinoma (ESCC) is unknown. This study investigates the role of PEDF in ESCC cell proliferation, migration, and cell cycle both in vitro and in vivo. The PEDF expression was examined in patient tumor samples and ESCC cell lines. Short hairpin RNA technology was used to inhibit the PEDF expression in ESCC EC9706 and KYSE150 cells. In vitro cell proliferation and migration assays were performed. The effects of PEDF on tumor growth and progression were examined in vivo in murine subcutaneous xenograft tumor models. It was found that PEDF was overexpressed in esophageal cancer cells and patient tumor tissues compared to normal control samples. PEDF enhanced cell cycle progression and inhibited cell apoptosis. Knock down of PEDF inhibited esophageal cell proliferation and migration in vitro. Moreover, Inhibition of PEDF significantly reduced tumor growth and tumor size in vivo. These results indicate that PEDF induce tumorigenesis in ESCC and can be a potential therapeutic target for cancer treatment.

show abstract

“…is a tumour suppressor in many types of cancer. [16][17][18][19][20][21] However, the study the intracellular mechanisms of action of therapeutic agents. 39,40,44 In the present study, HR8348 and SW837 cells were used to evaluate the effects of TIPE2 both in vitro and in vivo and A recent study has shown that TIPE2 overexpression could induce cell death and inhibit Ras-mediated tumourigenesis in mice.…”

Section: An Increasing Number Of Studies Have Demonstrated That Tipe2mentioning

confidence: 99%

Tumour necrosis factor‐α‐induced protein 8‐like 2 is a novel regulator of proliferation, migration, and invasion in human rectal adenocarcinoma cells

Liu

Gao

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

Tumour necrosis factor‐α‐induced protein 8‐like 2 (TIPE2) is a tumour suppressor in many types of cancer. However, the mechanism of action of TIPE2 on the growth of rectal adenocarcinoma is unknown. Our results showed that the expression levels of TIPE2 in human rectal adenocarcinoma tissues were higher than those in adjacent non‐tumour tissues. Overexpression of TIPE2 reduced the proliferation, migration, and invasion of human rectal adenocarcinoma cells and down‐regulation of TIPE2 showed reverse effects. TIPE2 overexpression increased apoptosis through down‐regulating the expression levels of Wnt3a, phospho (p)‐β‐Catenin, and p‐glycogen synthase kinase‐3β in rectal adenocarcinoma cells, however, TIPE2 knockdown exhibited reverse trends. TIPE2 overexpression decreased autophagy by reducing the expression levels of p‐Smad2, p‐Smad3, and transforming growth factor‐beta (TGF‐β) in rectal adenocarcinoma cells, however, TIPE2 knockdown showed opposite effects. Furthermore, TIPE2 overexpression reduced the growth of xenografted human rectal adenocarcinoma, whereas TIPE2 knockdown promoted the growth of rectal adenocarcinoma tumours by modulating angiogenesis. In conclusion, TIPE2 could regulate the proliferation, migration, and invasion of human rectal adenocarcinoma cells through Wnt/β‐Catenin and TGF‐β/Smad2/3 signalling pathways. TIPE2 is a potential therapeutic target for the treatment of rectal adenocarcinoma.

show abstract

TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/β-catenin pathway

Cited by 20 publications

References 35 publications

TZAP plays an inhibitory role in the self-renewal of porcine mesenchymal stromal cells and is implicated the regulation of premature senescence via the p53 pathway

TZAP plays an inhibitory role in the self-renewal of porcine mesenchymal stromal cells and is implicated the regulation of premature senescence via the p53 pathway

Pigment Epithelium-Derived Factor Promotes the Growth and Migration of Human Esophageal Squamous Cell Carcinoma

Tumour necrosis factor‐α‐induced protein 8‐like 2 is a novel regulator of proliferation, migration, and invasion in human rectal adenocarcinoma cells

Contact Info

Product

Resources

About