TIPE2 inhibits TNF-α-induced hepatocellular carcinoma cell metastasis via Erk1/2 downregulation and NF-κB activation

Zhang, Yue Hua; Hong, Yan; Fang, Wang; Wang, Yan Yan; Jiang, Yi; Wang, Yi Nan; Gao, Feng

doi:10.3892/ijo.2014.2725

Cited by 48 publications

(31 citation statements)

References 39 publications

(54 reference statements)

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“…56 It also inhibits the TNFmediated activation of Erk1/2 and NF-κB in an HCC cell line. 68 In contrast, TIPE2 overexpression induced cell death and inhibited Ras-mediated tumorigenesis in mice. 23 In gastric cell lines, increased TIPE2 expression decreased cell proliferation by upregulating N-ras and p27 expression, 53 the latter of which is mediated by interferon regulatory factor 4 via NF-κB; 69 TIPE2 has also been found to regulate AKT and ERK1/2 signaling in these cells 70 as well as GSK3β and downstream β-catenin translocation.…”

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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“…Additionally, a study on HCC showed NF-κB to be involved in TIPE2 mediated lung cancer. TIPE2 suppressed TNF-α induced metastasis of HCC cells via inhibition of NF-κB and ERK1/2 [27]. In addition, TIPE2 also exerted its function through regulation of autophagy, as LC-3B was downregulated in TIPE2 knockout cells.…”

Section: Discussionmentioning

confidence: 97%

“…Moreover, adenovirus-mediated human TIPE2 gene transfer (AdVTIPE2) led to the suppression of gastric cancer cells' growth through decreased Akt, ERK1/2, and activation of the intrinsic apoptotic pathway [26]. Besides, TIPE2 suppressed TNF-α-mediated metastasis of hepatocellular carcinoma (HCC) cells by inhibiting nuclear factor kappa B (NF-κB) and Erk1/2, indicating TIPE2 as a plausible target against HCC metastasis [27]. Further, in the case of NSCLC tissues, TIPE2 was found to be upregulated, which exerted a negative correlation with primary tumor size, lymph node metastasis, and advanced clinical stage of the disease [28].…”

Section: Introductionmentioning

confidence: 99%

TIPE2 Induced the Proliferation, Survival, and Migration of Lung Cancer Cells Through Modulation of Akt/mTOR/NF-κB Signaling Cascade

et al. 2019

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Lung cancer represents the most common cause of cancer deaths in the world, constituting around 11.6% of all new cancer cases and 18.4% of cancer-related deaths. The propensity for early spread, lack of suitable biomarkers for early diagnosis, as well as prognosis and ineffective existing therapies, contribute to the poor survival rate of lung cancer. Therefore, there is an urgent need to develop novel biomarkers for early diagnosis and prognosis which in turn can facilitate newer therapeutic avenues for the management of this aggressive neoplasm. TIPE2 (tumor necrosis factor-α-induced protein 8-like 2), a recently identified cytoplasmic protein, possesses enormous potential in this regard. Immunohistochemical analysis showed that TIPE2 was significantly upregulated in different stages and grades of lung cancer tissues compared to normal lung tissues, implying its involvement in the positive regulation of lung cancer. Further, knockout of TIPE2 resulted in significantly reduced proliferation, survival, and migration of human lung cancer cells through modulation of the Akt/mTOR/NF-κB signaling axis. In addition, knockout of TIPE2 also caused arrest in the S phase of the cell cycle of lung cancer cells. As tobacco is the most predominant risk factor for lung cancer, we therefore evaluated the effect of TIPE2 in tobacco-mediated lung carcinogenesis as well. Our results showed that TIPE2 was involved in nicotine-, nicotine-derived nitrosamine ketone (NNK)-, N-nitrosonornicotine (NNN)-, and benzo[a]pyrene (BaP)-mediated lung cancer through inhibited proliferation, survival, and migration via modulation of nuclear factor kappa B (NF-κB)- and NF-κB-regulated gene products, which are involved in the regulation of diverse processes in lung cancer cells. Taken together, TIPE2 possesses an important role in the development and progression of lung cancer, particularly in tobacco-promoted lung cancer, and hence, specific targeting of it holds an enormous prospect in newer therapeutic interventions in lung cancer. However, these findings need to be validated in the in vivo and clinical settings to fully establish the diagnostic and prognostic importance of TIPE2 against lung cancer.

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“…At the same time, numerous studies have shown that the TNFAIP8 family is associated with the development of multiple tumors.TNFAIP8 has been demonstrated to be upregulated in NSCLC tumor tissues, gastric adenocarcinoma tissues, platinumresistant epithelial ovarian cancer tissues, and endometrial cancer tissues [10][11][12][13]. TIPE2 expression was more pronounced in colon cancer tissues, but downregulated in HCC [14,15].…”

Section: Discussionmentioning

confidence: 99%

The Expression and Significance of TIPE1 in Lichen Planus

Yang¹,

Zheng²,

Changji³

et al. 2018

CRDOA

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Background: Lichen Planus (LP) is a common inflammatory skin disease. Studies have shown that TIPE1 may play an important role in the immune, endocrine and the formation of the tumor. However to our knowledge, there are few reports about the role of TIPE1 in inflammatory diseases. Methods/Design: Immunohistochemistry was carried out to examine the expression of TIPE1 in tissue specimens from the lesions of 40 patients with LP, as well as from the skin of 35 normal human controls. Results: In this study, we found that TIPE1 expression was elevated in the epidermis layer in samples of LP versus normal skin, but reduced in the liquefaction degeneration of basal layer and the lichenoid infiltration of lymphocytes in the papillary dermis. Conclusion: Our results suggested that TIPE1 is involved in the occurrence and development of LP and that it may serve as a biomarker or therapeutic target of this disease.

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TIPE2 inhibits TNF-α-induced hepatocellular carcinoma cell metastasis via Erk1/2 downregulation and NF-κB activation

Cited by 48 publications

References 39 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 Induced the Proliferation, Survival, and Migration of Lung Cancer Cells Through Modulation of Akt/mTOR/NF-κB Signaling Cascade

The Expression and Significance of TIPE1 in Lichen Planus

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