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Review
. 2015 Feb 25;16(3):4471-91.
doi: 10.3390/ijms16034471.

Tumor Progression Locus 2 (Tpl2) Kinase as a Novel Therapeutic Target for Cancer: Double-Sided Effects of Tpl2 on Cancer

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Free PMC article
Review

Tumor Progression Locus 2 (Tpl2) Kinase as a Novel Therapeutic Target for Cancer: Double-Sided Effects of Tpl2 on Cancer

Hye Won Lee et al. Int J Mol Sci. .
Free PMC article

Abstract

Tumor progression locus 2 (Tpl2) is a mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) that conveys various intra- and extra-cellular stimuli to effector proteins of cells provoking adequate adoptive responses. Recent studies have elucidated that Tpl2 is an indispensable signal transducer as an MAP3K family member in diverse signaling pathways that regulate cell proliferation, survival, and death. Since tumorigenesis results from dysregulation of cellular proliferation, differentiation, and apoptosis, Tpl2 participates in many decisive molecular processes of tumor development and progression. Moreover, Tpl2 is closely associated with cytokine release of inflammatory cells, which has crucial effects on not only tumor cells but also tumor microenvironments. These critical roles of Tpl2 in human cancers make it an attractive anti-cancer therapeutic target. However, Tpl2 contradictorily works as a tumor suppressor in some cancers. The double-sided effects of Tpl2 originate from the specific upstream and downstream signaling environment of each tumor, since Tpl2 interacts with various signaling components. This review summarizes recent studies concerning the possible roles of Tpl2 in human cancers and considers its possibility as a therapeutic target, against which novel anti-cancer agents could be developed.

Figures

Figure 1
Figure 1
The typical MAPK signaling pathways mediating the transmission of external signals to intra-cellular effector proteins. MAP4K: mitogen-activated protein kinase kinase kinase kinase; MAP3K: mitogen-activated protein kinase kinase kinase; MAP2K: mitogen-activated protein kinase kinase; MAPK: mitogen-activated protein kinase.
Figure 2
Figure 2
Tpl2 mediated signaling cascades involved in cancer development and progression.

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References

    1. Yang S.H., Sharrocks A.D., Whitmarsh A.J. Transcriptional regulation by the map kinase signaling cascades. Gene. 2003;320:3–21. doi: 10.1016/S0378-1119(03)00816-3. - DOI - PubMed
    1. Whitmarsh A.J. Regulation of gene transcription by mitogen-activated protein kinase signaling pathways. Biochim. Biophys. Acta. 2007;1773:1285–1298. doi: 10.1016/j.bbamcr.2006.11.011. - DOI - PubMed
    1. Krishna M., Narang H. The complexity of mitogen-activated protein kinases (Mapks) made simple. Cell. Mol. Life Sci. 2008;65:3525–3544. doi: 10.1007/s00018-008-8170-7. - DOI - PubMed
    1. Wang X., Tournier C. Regulation of cellular functions by the ERK5 signalling pathway. Cell. Signal. 2006;18:753–760. doi: 10.1016/j.cellsig.2005.11.003. - DOI - PubMed
    1. Pritchard A.L., Hayward N.K. Molecular pathways: Mitogen-activated protein kinase pathway mutations and drug resistance. Clin. Cancer Res. 2013;19:2301–2309. doi: 10.1158/1078-0432.CCR-12-0383. - DOI - PubMed

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