TIPE2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Prostate Cancer Cells by Inhibiting PI3K/Akt Signaling Pathway

Lü, Qiang; Liu, Zhe; Li, Zhuo; Chen, Jia; Liao, Zhiwei; Wu, Wanrui; Li, Yuanwei

doi:10.3727/096504016x14666990347437

Cited by 39 publications

(39 citation statements)

References 24 publications

(10 reference statements)

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“…Overexpression of TIPE2 in tumor cells can induce cell death and significantly inhibit Ras-induced tumorigenesis in mice (Gus-Brautbar et al, 2012). TIPE2 regulates cell death by binding to the Ras-interacting domain of RGL (Ral GDP dissociation stimulator-like) and inhibiting the activation of the downstream signaling molecules Ral and AKT (Gus-Brautbar et al, 2012;Lu et al, 2016;Sun et al, 2012;Wang et al, 2012). In this manner, TIPE2 acts as a molecular bridge between inflammation and cancer.…”

Section: Introductionmentioning

confidence: 99%

TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis

Yan

Wang

Sun

et al. 2019

Journal of Experimental Medicine

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Myeloid-derived suppressor cells (MDSCs) are “polarized” myeloid cells that effectively promote tumorigenesis by inhibiting antitumor immunity. How myeloid cells acquire the protumoral properties during tumorigenesis is poorly understood. We report here that the polarity protein TIPE2 (tumor necrosis factor-α–induced protein 8-like 2) mediates the functional polarization of murine and human MDSCs by specifying their pro- and antitumoral properties. Tumor cells induced the expression of TIPE2 in Gr1+CD11b+ cells through reactive oxygen species (ROS). TIPE2 in turn increased the expression of protumoral mediators such as CCAAT/enhancer-binding protein-β while inhibiting the expression of antitumoral mediators. Consequently, tumor growth in TIPE2-deficient mice was significantly diminished, and TIPE2-deficient MDSCs markedly inhibited tumor growth upon adoptive transfer. Pharmaceutical blockade of ROS inhibited TIPE2 expression in MDSCs and reduced tumor growth in mice. These findings indicate that TIPE2 plays a key role in the functional polarization of MDSCs and represents a new therapeutic target for cancer immunotherapy.

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Section: Introductionmentioning

confidence: 99%

TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis

Yan

Wang

Sun

et al. 2019

Journal of Experimental Medicine

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“…Decreased TIPE2 expression were previously reported in a number of tumors such as hepatocellular carcinoma (HCC), gastric cancer, glioma and prostate cancer [14, 15, 17, 32]. However, increased TIPE2 expression was also observed in some specific tumors including colorectal cancer (CRC), non-small cell lung cancer (NSCLC) and skin squamous cancer [16, 33, 34].…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that TIPE2 may function as a tumor suppressor by inhibiting several classic oncogenic signaling pathways [15, 17]. Our previous research demonstrated that TIPE2 suppressed the migration and invasion of HCC and NSCLC cells by inhibiting Rac1 [14, 16].…”

Section: Discussionmentioning

confidence: 99%

TIPE2 acts as a biomarker for tumor aggressiveness and suppresses cell invasiveness in papillary thyroid cancer (PTC)

Jia

Chen

et al. 2018

Cell Biosci

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BackgroundTumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TIPE2 or TNFAIP8L2) is a newly described negative immune regulator and is closely associated with various tumors. However, the expression and roles of TIPE2 in PTC is unknown.ResultsIn the present study, TIPE2 upregulation in PTC tissues was found to be negatively associated with tumor size, capsule infiltration, peripheral infiltration and tumor T stage, which could be used to predict tumor invasiveness. TIPE2 overexpression significantly suppressed the viability, proliferation, migration and invasion of PTC cells. Moreover, TIPE2 suppressed tumor invasiveness by inhibiting Rac1, leading to decreased expression of uPA and MMP9.ConclusionsThese results indicate that TIPE2 is a potential biomarker for predicting tumor aggressiveness and suppresses tumor invasiveness in a Rac1-dependent manner.Electronic supplementary materialThe online version of this article (10.1186/s13578-018-0247-x) contains supplementary material, which is available to authorized users.

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“…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]. In addition, TIPE2 overexpression led to decreased migration, invasion, and EMT in prostate cancer cells through PI3K/Akt inhibition [29].…”

Section: Introductionmentioning

confidence: 93%

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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TIPE2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Prostate Cancer Cells by Inhibiting PI3K/Akt Signaling Pathway

Cited by 39 publications

References 24 publications

TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis

TIPE2 specifies the functional polarization of myeloid-derived suppressor cells during tumorigenesis

TIPE2 acts as a biomarker for tumor aggressiveness and suppresses cell invasiveness in papillary thyroid cancer (PTC)

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

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