TNFAIP8 regulates Hippo pathway through interacting with LATS1 to promote cell proliferation and invasion in lung cancer

Ye, Han; Tang, Zhongping; Zhao, Yue; Li, Qingchang; Wang, Enhua

doi:10.1002/mc.22740

Cited by 25 publications

(30 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Overexpression of YAP in EOC cells efficiently attenuated cell growth inhibition in TNFAIP8-deficient EOC cells. These data are consistent with those of previous studies that demonstrated the regulatory role of TNFAIP8 in Hippo signaling ( 28 , 29 ). Additional experimental studies also suggest the involvement of TNFAIP8 in apoptosis and cell cycle checkpoint protein expression in EOC cells, which were identified as downstream targets of YAP ( 7 , 8 ).…”

Section: Discussionsupporting

confidence: 93%

“…Dai et al ( 26 ) demonstrated that TNFAIP8 upregulated cell proliferation, migration, invasion, and xenograft tumor growth in HCC cells. TNFAIP8 also promoted cell proliferation and invasion in lung cancer ( 29 ). Concurrently, downregulated expression of TNFAIP8 via the overexpression of microRNA (miR)-9 markedly inhibited gastric cancer cell proliferation in vitro and tumor growth in vivo ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

TNFAIP8 promotes cell growth by regulating the Hippo pathway in epithelial ovarian cancer

2018

View full text Add to dashboard Cite

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is an independent prognostic factor for cancer-specific and disease-free survival in patients with epithelial ovarian cancer (EOC). However, the exact mechanism of the biological role of TNFAIP8 in EOC remains unclear. In the present study, a siRNA specifically targeting TNFAIP8 was prepared to knock down TNFAIP8 in EOC cells. Cell growth, colony formation, apoptosis, and cell cycle distribution in TNFAIP8-deficient EOC cells were determined. In addition, the underlying molecular mechanisms were investigated by western blot analysis and reverse transcription quantitative polymerase chain reaction assays. It was demonstrated that the knockdown of TNFAIP8 inhibited EOC cell growth and colony formation, along with increased levels of apoptosis and cell cycle arrest. The results of the western blot analysis suggested that TNFAIP8 inhibited the expression of phosphorylated yes-associated protein 1 (YAP) while promoting total and nuclear YAP expression, followed by the regulation of apoptosis and cell cycle checkpoint protein expression in EOC. Overexpression of YAP in EOC cells efficiently attenuated cell growth inhibition in TNFAIP8-deficient EOC cells. In addition, knockdown of TNFAIP8 significantly impaired EOC tumor growth in vivo. Collectively, the data from the present study suggested that TNFAIP8 is an oncogene and a novel therapeutic target for EOC.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

TNFAIP8 promotes cell growth by regulating the Hippo pathway in epithelial ovarian cancer

2018

View full text Add to dashboard Cite

show abstract

“…The gene is located on chromosome 5q23.1 and is expressed in most malignant foot tumor tissues. Studies on these tumors have all suggested that signal transduction pathway affects many processes such as cell apoptosis, and therefore plays an important role in the formation and development of tumors [8]. In recent years, a series of functions of TNFAIP 8 in tumor formation have been continuously con rmed.…”

Section: Introductionmentioning

confidence: 99%

TNFAIP8 inhibits gastric cancer proliferation by mTOR-Akt-ULK1 and autophagy signal pathway

Chen

Zhang²,

Dong

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The purpose of this article was to study the role of TNFAIP8 in gastric cancer.Methods: RT-PCR was used to detect the expression of TNFAIP8 mRNA and protein level in normal gastric mucosa cells and four gastric cancer (GC) cell lines. TNFAIP8 was silenced or overexpressed in two cell lines, CCK-8 cell viability was used, transwell experiment was used to detect cell invasion capability, and flow cytometry was used to detect cell apoptosis. TNFAIP was silenced or overexpressed in a cell line, and nude mice were inoculated to form transplanted tumors. HE staining and immunohistochemistry staining were used to detect the histopathological changes of tumors. Results: The mRNA and protein expression of TNFAIP8 was significantly up-regulated in GC patients and cells. After silencing and overexpressing TNFAIP8, GC cells with high expression increased, apoptosis decreased, and cell invasion increased. Expression of mTOR-Akt-ULK1 signal pathway was inhibited and autophagy signal was activated. Conclusions: Our findings indicate that TNFAIP8 inhibited GC cells by inhibiting mTOR-Akt-ULK1 signal pathway and activating autophagy signal.

show abstract

“…Expression of transcriptional coactivator and a Hippo pathway effector YAP1 has been associated with resistance to TKI and BRAF inhibitors, upregulation of PD-L1, and poor survival in NSCLC (23,24). TNFAIP8 has been shown to interact with LATS1, one of the Hippo core components, and promote nuclear localization of YAP and expression of downstream targets cyclin D1 and CDK6 in lung cancer cells (25).…”

Section: Introductionmentioning

confidence: 99%

Dual Targeting of EGFR and IGF1R in the TNFAIP8 Knockdown Non–Small Cell Lung Cancer Cells

Day

Kallakury

Ross

et al. 2019

Molecular Cancer Research

View full text Add to dashboard Cite

Aberrant regulation of EGFR is common in non-small cell lung carcinomas (NSCLC), and tumor resistance to targeted therapies has been attributed to emergence of other cooccurring oncogenic events, parallel bypass receptor tyrosine kinase pathways including IGF1R, and TNFadriven adaptive response via NF-kB. TNFAIP8, TNFa-inducible protein 8, is an NF-kB-activated prosurvival and oncogenic molecule. TNFAIP8 expression protects NF-kB-null cells from TNFa-induced cell death by inhibiting caspase-8 activity. Here, we demonstrate that knockdown of TNFAIP8 inhibited EGF and IGF-1-stimulated migration in NSCLC cells. TNFAIP8 knockdown cells showed decreased level of EGFR and increased expression of sorting nexin 1 (SNX1), a key regulator of the EGFR trafficking through the endosomal compartments, and treatment with SNX1 siRNA partially restored EGFR expression in these cells. TNFAIP8 knockdown cells also exhibited downregulation of IGF-1-induced pIGF1R and pAKT, and increased expression of IGF-1-binding protein 3 (IGFBP3), a negative regulator of the IGF-1/IGF1R signaling. Consistently, treatment of TNFAIP8 knockdown cells with IGFBP3 siRNA restored pIGF1R and pAKT levels. TNFAIP8 knockdown cells had enhanced sensitivities to inhibitors of EGFR, PI3K, and AKT. Furthermore, IHC expression of TNFAIP8 was associated with poor prognosis in NSCLC. These findings demonstrate TNFAIP8-mediated regulation of EGFR and IGF1R via SNX1 and IGFBP3, respectively. We posit that TNFAIP8 is a viable, multipronged target downstream of the TNFa/NF-kB axis, and silencing TNFAIP8 may overcome adaptive response in NSCLC. Implications: TNFAIP8 and its effectors SNX1 and IGFBP3 may be exploited to improve the efficacy of molecular-targeted therapies in NSCLC and other cancers.

show abstract

TNFAIP8 regulates Hippo pathway through interacting with LATS1 to promote cell proliferation and invasion in lung cancer

Cited by 25 publications

References 24 publications

TNFAIP8 promotes cell growth by regulating the Hippo pathway in epithelial ovarian cancer

TNFAIP8 promotes cell growth by regulating the Hippo pathway in epithelial ovarian cancer

TNFAIP8 inhibits gastric cancer proliferation by mTOR-Akt-ULK1 and autophagy signal pathway

Dual Targeting of EGFR and IGF1R in the TNFAIP8 Knockdown Non–Small Cell Lung Cancer Cells

Contact Info

Product

Resources

About