PTPL1 suppresses lung cancer cell migration via inhibiting TGF-β1-induced activation of p38 MAPK and Smad 2/3 pathways and EMT

Zhu, Ning; Zhang, Xiujuan; Zou, Hai; Zhang, Yuanyuan; Xia, Jie; Zhang, Peng; You-zhi, Zhang; Li, Jing; Dong, Liang; Wumaier, Gulinuer; Li, Shengqing

doi:10.1038/s41401-020-00596-y

Cited by 15 publications

(9 citation statements)

References 36 publications

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“…Recent studies revealed that TGF-β accelerated the invasive and migratory potential through the induction of EMT via the ERK pathway in breast cancer cells [ 57 ] and glioma cells [ 58 ]. In addition, TGF-β induced the EMT process through the p38 pathway in metastatic lung cancer [ 59 , 60 ] and cervical cancer cells [ 61 ]. Moreover, JNK signaling is also associated with TGF-β-induced EMT in various cancer cells [ 62 , 63 ].…”

Section: Discussionmentioning

confidence: 99%

GLUT3 Promotes Epithelial–Mesenchymal Transition via TGF-β/JNK/ATF2 Signaling Pathway in Colorectal Cancer Cells

et al. 2022

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Glucose transporter (GLUT) 3, a member of the GLUTs family, is involved in cellular glucose utilization and the first step in glycolysis. GLUT3 is highly expressed in colorectal cancer (CRC) and it leads to poor prognosis to CRC patient outcome. However, the molecular mechanisms of GLUT3 on the epithelial–mesenchymal transition (EMT) process in metastatic CRC is not yet clear. Here, we identified that activation of the c-Jun N-terminal kinase (JNK)/activating transcription factor-2 (ATF2) signaling pathway by transforming growth factor-β (TGF-β) promotes GLUT3-induced EMT in CRC cells. The regulation of GLUT3 expression was significantly associated with EMT-related markers such as E-cadherin, α- smooth muscle actin (α-SMA), plasminogen activator inhibitor-1 (PAI-1), vimentin and zinc finger E-box binding homeobox 1 (ZEB1). We also found that GLUT3 accelerated the invasive ability of CRC cells. Mechanistically, TGF-β induced the expression of GLUT3 through the phosphorylation of JNK/ATF2, one of the SMAD-independent pathways. TGF-β induced the expression of GLUT3 by increasing the phosphorylation of JNK, the nuclear translocation of the ATF2 transcription factor, and the binding of ATF2 to the promoter region of GLUT3, which increased EMT in CRC cells. Collectively, our results provide a new comprehensive mechanism that GLUT3 promotes EMT process through the TGF-β/JNK/ATF2 signaling pathway, which could be a potential target for the treatment of metastatic CRC.

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Section: Discussionmentioning

confidence: 99%

GLUT3 Promotes Epithelial–Mesenchymal Transition via TGF-β/JNK/ATF2 Signaling Pathway in Colorectal Cancer Cells

et al. 2022

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“…Epithelial-mesenchymal transition (EMT) enables the dissemination and distal metastasis of primary tumors. It has been widely reported that the p38 MAKP signaling pathway is frequently associated with the EMT progression in breast cancer and lung cancer [ 43 , 44 ]. Yuan et al found that gelsolin could suppress the metastasis of gastric cancer through inhibition of PKR-p38 signaling [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

circFAM120B functions as a tumor suppressor in esophageal squamous cell carcinoma via the miR-661/PPM1L axis and the PKR/p38 MAPK/EMT pathway

et al. 2022

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Extensive changes of circRNA expression underscore their essential contributions to multiple hallmarks of cancers; however, their functions and mechanisms of action in esophageal squamous cell carcinoma (ESCC) remain undetermined. Here, we adopted a three-stage approach by first screening for significantly differentially expressed circRNAs in ESCC and performing an external validation study, followed by the functional analyses. The properties of circRNAs were evaluated using Sanger sequencing, RNase R digestion, actinomycin D treatment, subcellular localization analysis, and fluorescence in situ hybridization. Target transcripts were predicted using online tools and verified by dual-luciferase, RNA immunoprecipitation, qRT-PCR, and western blot. Biotin-labeled RNA-protein pull-down, mass spectrometry, and RNA immunoprecipitation were employed to identify proteins interacting with circRNAs. Gain- and loss-of-function experiments were performed to uncover the roles of circRNAs, their target genes, and binding proteins in the proliferation, metastasis, and invasion. We observed that circFAM120B (hsa_circ_0001666) was frequently downregulated in cancer tissues and patient plasma, and its expression level was related to overall survival in ESCC patients. Overexpression of circFAM120B inhibited the proliferation, metastasis, and invasion of ESCC while silencing it enhanced malignant phenotypes. Mechanistically, circFAM120B was predominantly located in the cytoplasm, guarantying its sponging for miR-661 to restore the expression of PPM1L, a tumor suppressor. We observed that circFAM120B could reduce the stability of RNA-dependent protein kinase (PKR) by promoting its ubiquitination-dependent degradation and subsequently regulating the p38 MAPK signaling pathway, resulting in the repression of EMTs in ESCC cells. Our findings suggest that circFAM120B is a promising biomarker of ESCC, which acts as a tumor suppressor via the circFAM120B/miR-661/PPM1L axis and PKR/p38 MAPK/EMT pathway, supporting its significance as a candidate therapeutic target.

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“…Another breast cancer study showed that MAPK activation down-regulated E-cadherin expression and signi cantly increased EMT [21]. TGF-β and MAPK and their regulatory relationship to EMT have also been observed in different cell lines, such as lung cancer cell A549 and human proximal tubule cell HK-2 [22,23] . Membrane receptor phosphorylation and GSK3β inactivation in the Wnt pathway, followed by the release of β-catenin, activate target genes closely related to the EMT process [24].…”

Section: Introductionmentioning

confidence: 94%

Overexpression of RNF180 Inhibits Progression and Metastasis by Epithelial Mesenchymal Transformation and Immune Infiltration in Renal Cancer

Zhang

Tang

Guan

et al. 2022

Preprint

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Background: Molecular biomarkers combined with histopathological examination are of critical importance in the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC). The occurrence and development of ccRCC is closely related to abnormal E3 ubiquitin enzyme. Although recent studies have revealed that Ring Finger Protein 180 (RNF180)，known as an E3 ubiquitination enzyme, could regulate the cell proliferation, and differentiation in different cancers, the precise role of RNF180 in renal cancer remains to be elucidated. Methods: Western-blot, qPCR and CCK-8 assay were performed to initially explore and further validate the function of RNF180. The effect of RNF180 on cell migration and invasion was verified by Transwell assay and EdU assay. The morphology of the tissue slides was evaluated by HE staining and immunohistochemical assay. Cell line-derived xenograft models in mice further validated the effect of RNF180 in vivo. Bioinformatics tools based on public databases were used to assess patient survival and immune infiltration.Results: RNF180 is significantly down-regulated in multiple cancer-related databases and ccRCC cell lines. By using immunohistochemical analysis, we found that the expression level of RNF180 was also downregulated in ccRCC and the lower expression level of the RNF180 was associated with poorer clinical outcomes in renal cancer patients. Overexpression of RNF180 inhibits proliferation, migration and invasion of ccRCCs in vitro. In vivo, RNF180 could also modulate renal cancer progression in murine subcutaneous xenografts and liver metastasis. Strikingly, we further investigated the underlying mechanism and found that overexpression of RNF180 inhibited the progression of ccRCC by reducing epithelial-mesenchymal transformation (EMT) and may related to immune infiltration.Conclusion: These results indicated that RNF180 can be used as a new diagnostic marker and prognostic factor, and can be served as a therapeutic target for ccRCC.

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PTPL1 suppresses lung cancer cell migration via inhibiting TGF-β1-induced activation of p38 MAPK and Smad 2/3 pathways and EMT

Cited by 15 publications

References 36 publications

GLUT3 Promotes Epithelial–Mesenchymal Transition via TGF-β/JNK/ATF2 Signaling Pathway in Colorectal Cancer Cells

GLUT3 Promotes Epithelial–Mesenchymal Transition via TGF-β/JNK/ATF2 Signaling Pathway in Colorectal Cancer Cells

circFAM120B functions as a tumor suppressor in esophageal squamous cell carcinoma via the miR-661/PPM1L axis and the PKR/p38 MAPK/EMT pathway

Overexpression of RNF180 Inhibits Progression and Metastasis by Epithelial Mesenchymal Transformation and Immune Infiltration in Renal Cancer

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