MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and invasion

  • Authors:
    • Jingchun Gao
    • Matthew J. McConnell
    • Bin Yu
    • Jiannong Li
    • Justin M. Balko
    • Esther P. Black
    • Joseph O. Johnson
    • Mark C. Lloyd
    • Soner Altiok
    • Eric B. Haura
  • View Affiliations

  • Published online on: August 1, 2009     https://doi.org/10.3892/ijo_00000345
  • Pages: 337-345
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Abstract

Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in human cancer including lung cancer and has been implicated in transformation, tumorigenicity, and metastasis. One putative downstream gene regulated by Stat3 is MUC1 which also has important roles in tumorigenesis. We determined if Stat3 regulates MUC1 in lung cancer cell lines and what function MUC1 plays in lung cancer cell biology. We examined MUC1 expression in non-small cell lung cancer (NSCLC) cell lines and found high levels of MUC1 protein expression associated with higher levels of tyrosine phosphorylated STAT3. STAT3 knockdown downregulated MUC1 expression whereas constitutive STAT3 expression increased MUC1 expression at mRNA and protein levels. MUC1 knockdown induced cellular apoptosis concomitant with reduced Bcl-XL and sensitized cells to cisplatin treatment. MUC1 knockdown inhibited tumor growth and metastasis in an orthotopic mouse model of lung cancer by activating apoptosis and inhibiting cell proliferation in vivo. These results demonstrate that constitutively activated STAT3 regulates expression of MUC1, which mediates lung cancer cell survival and metastasis in vitro and in vivo. MUC1 appears to be a cooperating oncoprotein with multiple oncogenic tyrosine kinase pathways and could be an effective target for the treatment of lung cancer.

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August 2009
Volume 35 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Gao J, McConnell MJ, Yu B, Li J, Balko JM, Black EP, Johnson JO, Lloyd MC, Altiok S, Haura EB, Haura EB, et al: MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and invasion. Int J Oncol 35: 337-345, 2009.
APA
Gao, J., McConnell, M.J., Yu, B., Li, J., Balko, J.M., Black, E.P. ... Haura, E.B. (2009). MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and invasion. International Journal of Oncology, 35, 337-345. https://doi.org/10.3892/ijo_00000345
MLA
Gao, J., McConnell, M. J., Yu, B., Li, J., Balko, J. M., Black, E. P., Johnson, J. O., Lloyd, M. C., Altiok, S., Haura, E. B."MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and invasion". International Journal of Oncology 35.2 (2009): 337-345.
Chicago
Gao, J., McConnell, M. J., Yu, B., Li, J., Balko, J. M., Black, E. P., Johnson, J. O., Lloyd, M. C., Altiok, S., Haura, E. B."MUC1 is a downstream target of STAT3 and regulates lung cancer cell survival and invasion". International Journal of Oncology 35, no. 2 (2009): 337-345. https://doi.org/10.3892/ijo_00000345