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TGIF1 promoted the growth and migration of cancer cells in nonsmall cell lung cancer

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Tumor Biology

Abstract

Transforming growth factor beta-inducing factor 1 (TGIF1) was reported to be dysregulated in several types of cancer. However, its expression pattern and functions in nonsmall cell lung cancer (NSCLC) remained unknown. In the present study, the expression of TGIF1 was found to be elevated in the clinical NSCLC tissues. TGIF1 promoted the growth and migration of NSCLC cells, while knocking down the expression of TGIF1 inhibited the growth and migration of NSCLC cells. Moreover, downregulation of TGIF1 impaired the metastasis of NSCLC cells. In the study for the molecular mechanisms, it was found that TGIF1 positively regulated beta-catenin/TCF signaling. In summary, our study demonstrated the oncogenic role of TGIF1 in NSCLC, and TGIF1 might be a therapeutic target for NSCLC.

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References

  1. DeSantis CE, Lin CC, Mariotto AB, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252–71.

    Article  PubMed  Google Scholar 

  2. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.

    Article  PubMed  Google Scholar 

  3. Lee CK, Brown C, Gralla RJ, et al. Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis. J Natl Cancer Inst. 2012;105(9):595–605.

    Article  Google Scholar 

  4. Oxnard GR, Janjigian YY, Arcila ME, et al. Maintained sensitivity to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer recurring after adjuvant erlotinib or gefitinib. Clin Cancer Res. 2012;17(19):6322–8.

    Article  Google Scholar 

  5. Chen X, Song X, Yue W, et al. Fibulin-5 inhibits Wnt/beta-catenin signaling in lung cancer. Oncotarget. 2015. (Epub ahead of print)

  6. Chen X, Meng J, Yue W, et al. Fibulin-3 suppresses Wnt/beta-catenin signaling and lung cancer invasion. Carcinogenesis. 2012;35(8):1707–16.

    Article  Google Scholar 

  7. Chen Z, Li J, Li QS, et al. Suppression of PPN/MG61 attenuates Wnt/beta-catenin signaling pathway and induces apoptosis in human lung cancer. Oncogene. 2008;27(24):3483–8.

    Article  CAS  PubMed  Google Scholar 

  8. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell. 2011;149(6):1192–205.

    Article  Google Scholar 

  9. Macdonald BT, Semenov MV, He X. SnapShot: Wnt/beta-catenin signaling. Cell. 2007;131(6):1204.

    Article  CAS  PubMed  Google Scholar 

  10. Clevers H. Wnt/beta-catenin signaling in development and disease. Cell. 2006;127(3):469–80.

    Article  CAS  PubMed  Google Scholar 

  11. He W, He S, Wang Z, et al. Astrocyte elevated gene-1(AEG-1) induces epithelial-mesenchymal transition in lung cancer through activating Wnt/beta-catenin signaling. BMC Cancer. 2011;15:107.

    Article  Google Scholar 

  12. Yang Y, Liu L, Cai J, et al. DEPDC1B enhances migration and invasion of non-small cell lung cancer cells via activating Wnt/beta-catenin signaling. Biochem Biophys Res Commun. 2010;450(1):899–905.

    Article  Google Scholar 

  13. Teng Y, Wang X, Wang Y, Ma D. Wnt/beta-catenin signaling regulates cancer stem cells in lung cancer A549 cells. Biochem Biophys Res Commun. 2011;392(3):373–9.

    Article  Google Scholar 

  14. Nakatani Y, Masudo K, Miyagi Y, et al. Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules. Mod Pathol. 2002;15(6):617–24.

    Article  PubMed  Google Scholar 

  15. Hneino M, Francois A, Buard V, et al. The TGF-beta/Smad repressor TG-interacting factor 1 (TGIF1) plays a role in radiation-induced intestinal injury independently of a Smad signaling pathway. PLoS One. 2011;7(5):e35672.

    Article  Google Scholar 

  16. Powers SE, Taniguchi K, Yen W, et al. Tgif1 and Tgif2 regulate Nodal signaling and are required for gastrulation. Development. 2011;137(2):249–59.

    Article  Google Scholar 

  17. Richieri-Costa A, Ribeiro LA. Variable phenotypic manifestations of a K44N mutation in the TGIF gene. Brain Dev. 2008;30(3):203–5.

    Article  PubMed  Google Scholar 

  18. Cohen Jr MM. Holoprosencephaly: clinical, anatomic, and molecular dimensions. Birth Defects Res A Clin Mol Teratol. 2006;76(9):658–73.

    Article  CAS  PubMed  Google Scholar 

  19. Horie T, Ono K, Kinoshita M, et al. TG-interacting factor is required for the differentiation of preadipocytes. J Lipid Res. 2008;49(6):1224–34.

    Article  CAS  PubMed  Google Scholar 

  20. Yan L, Womack B, Wotton D, et al. Tgif1 regulates quiescence and self-renewal of hematopoietic stem cells. Mol Cell Biol. 2011;33(24):4824–33.

    Article  Google Scholar 

  21. Hamid R, Brandt SJ. Transforming growth-interacting factor (TGIF) regulates proliferation and differentiation of human myeloid leukemia cells. Mol Oncol. 2009;3(5-6):451–63.

    Article  CAS  PubMed  Google Scholar 

  22. Hu ZL, Wen JF, Shen M, Liu Y. Expressions of TGIF, MMP9 and VEGF proteins and their clinicopathological relationship in gastric cancer. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2006;31(1):70–4.

    CAS  PubMed  Google Scholar 

  23. Imoto I, Pimkhaokham A, Watanabe T, Saito-Ohara F, Soeda E, Inazawa J. Amplification and overexpression of TGIF2, a novel homeobox gene of the TALE superclass, in ovarian cancer cell lines. Biochem Biophys Res Commun. 2000;276(1):264–70.

    Article  CAS  PubMed  Google Scholar 

  24. Yeh BW, Wu WJ, Li WM, et al. Overexpression of TG-interacting factor is associated with worse prognosis in upper urinary tract urothelial carcinoma. Am J Pathol. 2011;181(3):1044–55.

    Article  Google Scholar 

  25. Zhang MZ, Ferrigno O, Wang Z, et al. TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis. Cancer Cell. 2012;27(4):547–60.

    Article  Google Scholar 

  26. Gao Y, Song C, Hui L, et al. Overexpression of RNF146 in non-small cell lung cancer enhances proliferation and invasion of tumors through the Wnt/beta-catenin signaling pathway. PLoS One. 2012;9(1):e85377.

    Article  Google Scholar 

  27. Li X, Cai L, Liang M, Wang Y, Yang J, Zhao Y. ING4 induces cell growth inhibition in human lung adenocarcinoma A549 cells by means of Wnt-1/beta-catenin signaling pathway. Anat Rec (Hoboken). 2008;291(5):593–600.

    Article  CAS  Google Scholar 

  28. Faresse N, Colland F, Ferrand N, Prunier C, Bourgeade MF, Atfi A. Identification of PCTA, a TGIF antagonist that promotes PML function in TGF-beta signalling. Embo J. 2008;27(13):1804–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim WS, Park C, Hong SK, Park BK, Kim HS, Park K. Microsatellite instability (MSI) in non-small cell lung cancer(NSCLC) is highly associated with transforming growth factor-beta type II receptor(TGF-beta RII) frameshift mutation. Anticancer Res. 2000;20(3A):1499–502.

    CAS  PubMed  Google Scholar 

  30. Cheng T, Hu C, Yang H, Cao L, An J. Transforming growth factor-beta-induced miR143 expression in regulation of non-small cell lung cancer cell viability and invasion capacity in vitro and in vivo. Int J Oncol. 2011;45(5):1977–88.

    Google Scholar 

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    Authors and Affiliations

    1. Department of Thoracic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, China

      Guo Xiang, Yang Yi, He Weiwei & Wu Weiming

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    1. Guo Xiang
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    2. Yang Yi
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    3. He Weiwei
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    4. Wu Weiming
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    Correspondence to Wu Weiming.

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    Guo Xiang and Yang Yi contributed equally to this work.

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    Xiang, G., Yi, Y., Weiwei, H. et al. TGIF1 promoted the growth and migration of cancer cells in nonsmall cell lung cancer. Tumor Biol. 36, 9303–9310 (2015). https://doi.org/10.1007/s13277-015-3676-8

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    • DOI: https://doi.org/10.1007/s13277-015-3676-8

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