A novel role of myosin VI in human prostate cancer

Thomas A. Dunn, Shenglin Chen, Dennis A. Faith, Jessica L. Hicks, Elizabeth A Platz, Yidong Chen, Charles M. Ewing, Jurga Sauvageot, William B Isaacs, Angelo Michael Demarzo, Jun Luo

Research output: Contribution to journalArticle

Abstract

Myosin VI is an actin motor that moves to the minus end of the polarized actin filament, a direction opposite to all other characterized myosins. Using expression microarrays, we identified myosin VI as one of the top genes that demonstrated cancer-specific overexpression in clinical prostate specimens. Protein expression of myosin VI was subsequently analyzed in arrayed prostate tissues from 240 patients. Notably, medium-grade prostate cancers demonstrated the most consistent cancer-specific myosin VI protein overexpression, whereas prostate cancers associated with more aggressive histological features continued to overexpress myosin VI but to a lesser extent. Myosin VI protein expression in cell lines positively correlated with the presence of androgen receptor. Small interference RNA-mediated myosin VI knockdown in the LNCaP human prostate cancer cell line resulted in impaired in vitro migration and soft-agar colony formation. Depletion of myosin VI expression was also accompanied by global gene expression changes reflective of attenuated tumorigenic potential, as marked by a nearly 10-fold induction of TXNIP (VDUP1), a tumor suppressor with decreased expression in prostate cancer specimens. These results support that myosin VI is critical in maintaining the malignant properties of the majority of human prostate cancers diagnosed today.

Original languageEnglish (US)
Pages (from-to)1843-1854
Number of pages12
JournalAmerican Journal of Pathology
Volume169
Issue number5
DOIs
StatePublished - Nov 2006

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Prostatic Neoplasms
Prostate
myosin VI
Cell Line
Proteins
Neoplasm Genes
Androgen Receptors
Myosins
RNA Interference
Actin Cytoskeleton
Agar
Actins
Neoplasms
Gene Expression

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

A novel role of myosin VI in human prostate cancer. / Dunn, Thomas A.; Chen, Shenglin; Faith, Dennis A.; Hicks, Jessica L.; Platz, Elizabeth A; Chen, Yidong; Ewing, Charles M.; Sauvageot, Jurga; Isaacs, William B; Demarzo, Angelo Michael; Luo, Jun.

In: American Journal of Pathology, Vol. 169, No. 5, 11.2006, p. 1843-1854.

Research output: Contribution to journalArticle

Dunn, TA, Chen, S, Faith, DA, Hicks, JL, Platz, EA, Chen, Y, Ewing, CM, Sauvageot, J, Isaacs, WB, Demarzo, AM & Luo, J 2006, 'A novel role of myosin VI in human prostate cancer', American Journal of Pathology, vol. 169, no. 5, pp. 1843-1854. https://doi.org/10.2353/ajpath.2006.060316
Dunn, Thomas A. ; Chen, Shenglin ; Faith, Dennis A. ; Hicks, Jessica L. ; Platz, Elizabeth A ; Chen, Yidong ; Ewing, Charles M. ; Sauvageot, Jurga ; Isaacs, William B ; Demarzo, Angelo Michael ; Luo, Jun. / A novel role of myosin VI in human prostate cancer. In: American Journal of Pathology. 2006 ; Vol. 169, No. 5. pp. 1843-1854.
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