TIF1γ inhibits lung adenocarcinoma EMT and metastasis by interacting with the TAF15/TBP complex

Su, Zhiyue; Sun, Zelong; Wang, Zhao; Wang, Shengjie; Wang, Yuxin; Jin, Ersuo; Li, Chang; Zhao, Jun; Liu, Zeyi; Zhou, Zhengyu; Wang, Yong; Chen, Xiaoyan; Liu, Xia; Li, Zhe; Zhang, Hong Tao

doi:10.1016/j.celrep.2022.111513

Cited by 15 publications

(12 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TAF15 was first identified as an RNA or DNA binding protein that was involved in RNAPII-dependent transcription, pre-mRNA splicing, mRNA transport and DNA repair 27 . However, TAF15 has an extended functions beyond RNA or DNA binding.…”

Section: Discussionmentioning

confidence: 99%

TAF15 promotes cell proliferation, migration and invasion of gastric cancer via activation of the RAF1/MEK/ERK signalling pathway

Guo

et al. 2023

Sci Rep

View full text Add to dashboard Cite

TATA-box-binding protein-associated Factor 15 (TAF15), a member of the FUS/EWS/TAF15 (FET) family, contributes to the progression of various tumours. However, the role and molecular mechanism of TAF15 in gastric cancer (GC) progression are still unknown. In this study, we found that TAF15 was significantly upregulated in GC tumour tissues and cell lines. Overexpression of TAF15 was associated with a larger tumour size, high pathologic stage and high T stage of GC. TAF15 knockdown suppressed the proliferation, migration and invasion of GC cells in vitro and inhibited the tumour growth in vivo. Additionally, TAF15 knockdown led to the significant reductions in the phosphorylation levels of RAF1, MEK and ERK1/2, while total RAF1, MEK and ERK1/2 exhibited no significant change in GC cell lines. In summary, TAF15 is overexpressed in GC tumour tissues and cell lines, and promotes cell proliferation, migration and invasion in GC via the RAF1/MEK/ERK signaling pathway, which suggests that TAF15 might be a potential molecular diagnostic marker or therapeutic target for GC.

show abstract

Section: Discussionmentioning

confidence: 99%

TAF15 promotes cell proliferation, migration and invasion of gastric cancer via activation of the RAF1/MEK/ERK signalling pathway

Guo

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The process of EMT stood out to our interest as its occurrence is one of the molecular mechanisms involved in cancer cell metastasis [ 26 ]. Including lung cancer, EMT could lead cancer to an advanced stage by interacting with TAF15/TBP complex and this process could be impeded by Transcriptional intermediary factor 1 γ (TIFγ) [ 27 ]. Another literature also discovered that quaking 5 (QKI-5), a protein which is involved in RNA translation, transcription and non-coding RNA processing could inhibits TGF-β-induced EMT in LUAD [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis reveals CCNA2 as Lung Adenocarcinoma hub gene and is associated with cell proliferation and epithelial- mesenchymal transition

Tan

Meng

Han

et al. 2023

Preprint

View full text Add to dashboard Cite

Lung adenocarcinoma (LUAD) is one of the malignant tumors worldwide. The purpose of this study is to identify the hub genes related to LUAD using bioinformatics analysis. Three gene expression datasets (GSE27262, GSE74706, GSE75037) were obtained from GEO database. Identification of DEGs was performed using GEO2R and constructed protein-protein interaction network using STRING and cytoscape. GO, KEGG and GSEA analysis were carried out through R package “clusterprofiler”. GEPIA was used to verify the survival of hub genes, UALCAN database and HPA database were used to determine protein expression, complemented by IHC staining results. Lastly, CCK-8 and colony formation assays were used to verify PC9 cell growth ability and we used western blot, Transwell and scratch wound assays for validation of PC9 cells migration and EMT markers. We identified 107 up-regulated genes and 344 down-regulated genes. Thirty hub genes were identified and the 12 hub genes with a rank of degrees > 30 are as follow: CCNA2, AURKA, HMMR, EZH2, TTK, TPX2, CCNB1, ANLN, ECT2, CEP55, MAD2L1 and PBK. CCNA2 as one of the genes having the highest node degree of 35 was chosen for subsequent analysis. Our findings indicated that high expression of CCNA2 had the highest enrichment effects on cell cycle and was associated with poor prognosis. CCK-8 and colony formation analysis further verified that CCNA2 contributed to the progression of LUAD and the protein expression was significantly elevated in tumor tissues compared to the normal lung tissues. In addition, high expression of CCNA2 is related to the EMT process and may play a role in EMT-induced metastasis in LUAD. Briefly, CCNA2 was identified as one of the hub genes and can promote lung cancer cell growth, migration and invasion via epithelial-mesenchymal transition. Moreover, could avail as a biomarker or therapeutic target to judge the prognosis of LUAD.

show abstract

“…Co-IP was performed as described previously 27 with some modification. Briefly, cells were grown on 10cm dishes and lysed with ice-cold IP buffer (50 mM Tris-HCl (pH 7.5), 150 mM NaCl, 0.5% NP-40, 10% glycerol) for 30 min.…”

Section: Co-immunoprecipitation (Co-ip)mentioning

confidence: 99%

“…The anti-Flag or anti-HA Co-IP products from HEK 293T cells transfected with Flag-mTOR or HA-P4HA2 were resolved on SDS-PAGE gel and then identified with Silver Staining Kit (CWBIO, CW2012S). The protocol was performed as previously described 27 .…”

Section: Protein Silver-staining Assaymentioning

confidence: 99%

See 1 more Smart Citation

Prolyl 4-hydroxylase alpha-2 directly activates mTOR kinase

Jin

Wang

Chen

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Mammalian target of rapamycin (mTOR) kinase functions as a central regulator of cell growth and metabolism, and its complexes mTORC1 and mTORC2 phosphorylate distinct substrates1-3. Dysregulation of mTOR signaling is commonly implicated in human diseases, including cancer4,5. Despite three decades of active research in mTOR, much remains to be determined1. In fact, how mTOR kinase is directly activated and recognize distinct substrates are still unknown. Here, we demonstrate that prolyl 4-hydroxylase alpha-2 (P4HA2) can hydroxylate mTOR protein and thereby activating mTOR signal. By performing co-immunoprecipitation, GST pull-down assays combined with mass spectrometry-based proteomic analysis in 293T cells, we found that P4HA2 binds directly to mTOR and hydroxylates one highly conserved proline 2341 (P2341) within a kinase domain of mTOR. Moreover, we discover that the hydroxylation of P2341 strengthens mTOR stability and allows mTOR to accurately recognize its substrates such as S6K and AKT. Our study reveals an undiscovered hydroxylation-regulatory mechanism by which P4HA2 directly activates mTOR kinase, providing insights for therapeutically targeting mTOR kinase-driven cancers.

show abstract

TIF1γ inhibits lung adenocarcinoma EMT and metastasis by interacting with the TAF15/TBP complex

Cited by 15 publications

References 61 publications

TAF15 promotes cell proliferation, migration and invasion of gastric cancer via activation of the RAF1/MEK/ERK signalling pathway

TAF15 promotes cell proliferation, migration and invasion of gastric cancer via activation of the RAF1/MEK/ERK signalling pathway

Bioinformatic analysis reveals CCNA2 as Lung Adenocarcinoma hub gene and is associated with cell proliferation and epithelial- mesenchymal transition

Prolyl 4-hydroxylase alpha-2 directly activates mTOR kinase

Contact Info

Product

Resources

About