This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, S.-W. Articles by Lee, J.-D. Search for Related Content PubMed PubMed Citation Articles by Kim, S.-W. Articles by Lee, J.-D.

Tid1 Negatively Regulates the Migratory Potential of Cancer Cells by Inhibiting the Production of Interleukin-8

¹ Department of Immunology, The Scripps Research Institute, La Jolla; ² Johnson and Johnson Pharmaceutical Research and Development, San Diego, California; and ³ Unité Institut National de la Sante et de la Recherche Medicale 540, Montpellier, France

Requests for reprints: Jiing-Dwan Lee, Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037. Phone: 858-784-8703; Fax: 858-784-8343; E-mail: jdlee{at}scripps.edu.

Tid1 is the human homologue of the Drosophila tumor suppressor, Tid56. Reducing the expression of Tid1 in MDA-MB231 breast cancer cells enhanced their migration without affecting their survival or growth rate. From microarray screening, we discovered that after Tid1 depletion, the mRNA level of interleukin-8 (IL-8) was significantly increased in these cancer cells, which consequently increased secretion of IL-8 protein by 3.5-fold. The enhanced migration of these Tid1-knockdown cells was blocked by reducing the IL-8 expression or by adding an IL-8 neutralizing antibody to the culture medium, suggesting that enhancement of cell motility in these Tid1-deficient cells is dependent on the de novo synthesis of IL-8. Subsequently, we found that abrogating the nuclear factor B binding site in the IL-8 promoter completely blocked the Tid1 depletion–induced IL-8 expression in the breast cancer cells. As increased IL-8 levels are known to promote tumor metastasis, we tested the effect of Tid1 knockdown on tumor metastasis and found that Tid1 depletion enhanced the metastasis of breast cancer cells in animals. Together, these results indicate that Tid1 negatively regulates the motility and metastasis of breast cancer cells, most likely through attenuation of nuclear factor B activity on the promoter of the IL8 gene.

This article has been cited by other articles:

				S. P. Lad, J. Li, J. da Silva Correia, Q. Pan, S. Gadwal, R. J. Ulevitch, and E. Li Cleavage of p65/RelA of the NF-{kappa}B pathway by Chlamydia PNAS, February 20, 2007; 104(8): 2933 - 2938. [Abstract] [Full Text] [PDF]

				B. Lu, N. Garrido, J. N. Spelbrink, and C. K. Suzuki Tid1 Isoforms Are Mitochondrial DnaJ-like Chaperones with Unique Carboxyl Termini That Determine Cytosolic Fate J. Biol. Chem., May 12, 2006; 281(19): 13150 - 13158. [Abstract] [Full Text] [PDF]