TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression

Liu, Qingqing; Zhang, Fengfeng; Wang, Fang; Qiu, Jinghua; Luo, Chao; Zhu, Guo-Yong; Liu, Yingfu

doi:10.1371/journal.pone.0126176

Cited by 32 publications

(42 citation statements)

References 25 publications

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“…52 In neoplastic studies, TIPE2 expression has been found to be decreased or completely lost in human hepatic cancer, 23 and reduced TIPE2 expression is associated with metastasis. It is also downregulated in gastric cancer tissues, 53 NSCLC tumors 54 and small cell lung cancer tumors, 55 and the levels of TIPE2 inversely correlate with NSCLC TNM staging. 54 Moreover, reduced TIPE2 expression is associated with metastasis of hepatic cancer.…”

Section: Tipe2 Is a Negative Regulator Of Immunity And Inflammationmentioning

confidence: 99%

Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins

Goldsmith

Chen

2017

Cell Mol Immunol

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The TIPE (tumor necrosis factor-α-induced protein 8-like) family are newly described regulators of immunity and tumorigenesis consisting of four highly homologous mammalian proteins: TNFAIP8 (tumor necrosis factor-α-induced protein 8), TIPE1 (TNFAIP8-like 1, or TNFAIP8L1), TIPE2 (TNFAIP8L2) and TIPE3 (TNFAIP8L3). They are the only known transfer proteins of the lipid secondary messengers PIP2 (phosphatidylinositol 4,5-bisphosphate) and PIP3 (phosphatidylinositol 3,4,5-trisphosphate). Cell-surface receptors, such as G-protein-coupled receptors and receptor tyrosine kinases, regulate inflammation and cancer via several signaling pathways, including the nuclear factor (NF)-κB and phosphoinositide-3 kinase (PI3K) pathways, the latter of which is upstream of both Akt and STAT3 activation. An expression analysis in humans demonstrated that the TIPE family is dysregulated in cancer and inflammation, and studies both in mice and in vitro have demonstrated that this family of proteins plays a critical role in tumorigenesis and inflammatory responses. In this review, we summarize the current literature for all four family members, with a special focus on the phenotypic manifestations present in the various knockout murine strains, as well as the related cell signaling that has been elucidated to date.

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Section: Tipe2 Is a Negative Regulator Of Immunity And Inflammationmentioning

confidence: 99%

Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins

Goldsmith

Chen

2017

Cell Mol Immunol

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“…The shRNA sequence was cloned into the GV102 vector with enhanced green fluorescent protein and the identity of the resulting construct was verified by sequencing. A549 and LTEP-a2 cells were transfected with shAnxa3 or control vector using Lipofectamine® 2000 transfection reagent (Life Technologies) and G418 was added to select the transfected cells as described previously [15]. The mRNA and protein levels of Anxa3 in all stably transfected cell lines were detected by quantitative PCR (qPCR) and western blotting, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Colony formation assay was performed as described in our previous study [15]. In brief, cells were seeded at a density of 500 cells per well in 6-well culture plates and cultured for about two weeks.…”

Section: Methodsmentioning

confidence: 99%

Annexin A3 Knockdown Suppresses Lung Adenocarcinoma

Liu

Zhang

et al. 2016

Analytical Cellular Pathology

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Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin.

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“…There is evidence that both p38 MAPK and JNK activation promote cell apoptosis in tumour cells under some circumstances [53][54][55]. There is also extensive evidence showing that NF-κB activation suppresses apoptosis, most likely because NF-κB promotes the synthesis of proteins that can protect cells from apoptosis [56][57][58][59].…”

Section: Melatonin Enhances the Effectiveness Of Cisplatin By Suppresmentioning

confidence: 99%

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

Liu

Fan

Chen

et al. 2015

Cell Physiol Biochem

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Background/Aims: Melatonin, synthesized by the pineal gland and released into the blood, appears to have antitumour properties; however, the mechanisms of its anti-cancer effects are largely unknown, especially in stomach cancer. Here, we explore the antitumour activity of melatonin in a gastric cancer cell line (AGS) and analyse its molecular mechanisms. Methods: AGS cells were treated with melatonin, and cell viability was assessed using a CCK-8 assay. Flow cytometry was performed to evaluate apoptosis, and protein expression was examined by Western blotting. Results: Melatonin significantly inhibited cell viability, clone formation, and cell migration and invasion and induced apoptosis in AGS cells. Moreover, MAPK pathways (p38, JNK and ERK) were activated by melatonin treatment, which also significantly increased caspase-3 cleavage and Bax protein expression and decreased Bcl-2 protein expression in a time-dependent manner. Our results demonstrate that p38 and JNK inhibitors (SB203580 and SP600125, respectively) prevented melatonin-induced apoptosis; thus, the propensity of p38 MAPK and JNK to promote apoptosis could be at least partly due to the inhibition of NF-κB p65 activation by p38 and JNK. Finally, melatonin was able to strengthen cisplatin-mediated antitumour effects in human gastric carcinoma cells by up-regulating the expression of Bax, down-regulating the expression of Bcl-2 and activating the caspase-dependent apoptotic pathway. Conclusion: Melatonin induced apoptosis in AGS cells by activating the caspase-dependent apoptotic pathway and by inhibiting the nuclear translocation of NF-κB p65, two processes that are regulated by p38 and JNK. Furthermore, melatonin significantly enhanced the anti-tumour effects of cisplatin, with low systemic toxicity. These new findings suggest that melatonin may act as a potent anti-tumour agent and may have great potential as an adjuvant therapy in the future.

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TIPE2 Inhibits Lung Cancer Growth Attributing to Promotion of Apoptosis by Regulating Some Apoptotic Molecules Expression

Cited by 32 publications

References 25 publications

Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins

Regulation of inflammation and tumorigenesis by the TIPE family of phospholipid transfer proteins

Annexin A3 Knockdown Suppresses Lung Adenocarcinoma

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

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