Downregulated TIPE2 is associated with poor prognosis and promotes cell proliferation in non-small cell lung cancer

Li, Yuexia; Li, Xiaohui; Liu, Gang; Sun, Rong; Wang, Lirui; Wang, Jing; Wang, Hongmin

doi:10.1016/j.bbrc.2014.12.080

Cited by 36 publications

(39 citation statements)

References 18 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%

“…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. 56 In contrast, TIPE2 expression was increased in the tumor tissues of patients with renal cell carcinoma and positively correlated with TNM staging.…”

Section: Tipe2 Is a Negative Regulator Of Immunity And Inflammationmentioning

confidence: 99%

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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%

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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“…Thus, TIPE2 may be a tumor-suppressor and its loss may facilitate human cancer progression. Indeed, accumulating evidence has highly suggested a pivotal role of TIPE2 in cancer [42][43][44][45]. However, the information about the cell-autonomous role of TIPE2 in human cancers is limited.…”

Section: Discussionmentioning

confidence: 99%

“…The dysregulation of TIPE2 has also been found to mediate diverse immunological diseases [37][38][39][40][41]. Recently, involvement of loss of TIPE2 has been suggested in the carcinogenesis of different cancer, including Non-small cell lung cancer [42], hepatocellular carcinoma [43,44], renal cell carcinoma [45], etc. However, whether TIPE2 may be involved in the pathogenesis of OS has not been reported.…”

Section: Introductionmentioning

confidence: 99%

TIPE2 Mediates the Suppressive Effects of Shikonin on MMP13 in Osteosarcoma Cells

Deng¹,

Feng²,

Deng³

2015

Cell Physiol Biochem

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Background/Aims: Osteosarcoma (OS) is a primary malignant bone tumor in humans, and is notorious mainly for its distal metastases. We have recently shown that Shikonin, an effective constituent extracted from Chinese medicinal herb, inhibits OS cell invasion through suppression of matrix metalloproteinase 13 (MMP13). However, the underlying mechanisms remain unknown. Methods: Here, we studied the levels of tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2) in OS cells upon Shikonin treatment. TIPE2 levels were adapted in OS cell lines through transfection with plasmids carrying transgene or short-hairpin interference RNA (shRNA), and the effects of TIPE2 adaptation on MMP13 and cell invasiveness were evaluated by RT-qPCR, Western blot, ELISA and transwell cell migration assay, respectively. TIPE2 levels in OS specimens from patients were examined and correlated with cancer metastases and patient survival. Results: We found that Shikonin dose-dependently decreased MMP13 levels, and increased TIPE2 levels in two OS cell lines, U2OS and SaOS-2. Overexpression of TIPE2 in U2OS significantly suppressed MMP13 levels and cell invasiveness. Depletion of TIPE2 in SaOS-2 cells significantly increased MMP13 levels and cell invasiveness. Moreover, TIPE2 levels in OS specimens were significantly decreased, compared to adjacent non-cancer bone tissue. Lower TIPE2 levels correlated with higher incidence of metastases and worse 5-year survival. Conclusion: TIPE2 mediates the suppressive effects of Shikonin on MMP13 in osteosarcoma cells, and TIPE2 may be a novel therapeutic target for OS.

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“…Each possess seven alpha helices that surround a hydrophobic core thought to play a significant role in lipid second messenger signaling [7, 8]. The TNFAIP8 and TNFAIP8L2 genes participate in immunity and inflammation [6, 9–12], while all members of the TNFAIP8 gene family have been associated with cancers of various types, including those affecting the stomach [13–18], liver [11, 17, 19–22], prostate [23], lung [7, 24, 25], esophagus [7, 24, 25], and cervix [7, 26]. Although the TNFAIP8 gene family has been associated with inflammation, immunity, and cancer, little is known about the mechanisms by which these genes function and the evolutionary origins of the family are not yet fully understood.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary divergence of the vertebrate TNFAIP8 gene family: Applying the spotted gar orthology bridge to understand ohnolog loss in teleosts

et al. 2017

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Comparative functional genomic studies require the proper identification of gene orthologs to properly exploit animal biomedical research models. To identify gene orthologs, comprehensive, conserved gene synteny analyses are necessary to unwind gene histories that are convoluted by two rounds of early vertebrate genome duplication, and in the case of the teleosts, a third round, the teleost genome duplication (TGD). Recently, the genome of the spotted gar, a holostean outgroup to the teleosts that did not undergo this third genome duplication, was sequenced and applied as an orthology bridge to facilitate the identification of teleost orthologs to human genes and to enhance the power of teleosts as biomedical models. In this study, we apply the spotted gar orthology bridge to help describe the gene history of the vertebrate TNFAIP8 family. Members of the TNFAIP8 gene family have been linked to regulation of immune function and homeostasis and the development of multiple cancer types. Through a conserved gene synteny analysis, we identified zebrafish orthologs to human TNFAIP8L1 and TNFAIP8L3 genes and two co-orthologs to human TNFAIP8L2, but failed to identify an ortholog to human TNFAIP8. Through the application of the orthology bridge, we determined that teleost orthologs to human TNFAIP8 genes were likely lost in a genome inversion event after their divergence from their common ancestor with spotted gar. These findings demonstrate the value of this enhanced approach to gene history analysis and support the development of teleost models to study complex questions related to an array of biomedical issues, including immunity and cancer.

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Downregulated TIPE2 is associated with poor prognosis and promotes cell proliferation in non-small cell lung cancer

Cited by 36 publications

References 18 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

TIPE2 Mediates the Suppressive Effects of Shikonin on MMP13 in Osteosarcoma Cells

Evolutionary divergence of the vertebrate TNFAIP8 gene family: Applying the spotted gar orthology bridge to understand ohnolog loss in teleosts

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