Mirk/Dyrk1b mediates cell survival in rhabdomyosarcomas

Stephen E. Mercer, Daina Z. Ewton, Sejal M Shah, Asghar Naqvi, Eileen Friedman

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Rhabdomyosarcoma is the most common sarcoma in children and is difficult to treat if the primary tumor is nonresectable or if the disease presents with metastases. The function of the serine/threonine kinase Mirk was investigated in this cancer. Mirk has both growth arrest and survival functions in terminally differentiating skeletal myoblasts. Maintenance of Mirk growth arrest properties would cause down-regulation of Mirk in transformed myoblasts. Alternatively, Mirk expression would be retained if rhabdomyosarcoma cells used Mirk survival capability. Mirk expression was significant in 12 of 16 clinical cases of rhabdomyosarcoma. Mirk was detected in each rhabdomyosarcoma cell line examined. Mirk was a functional kinase in each of three rhabdomyosarcoma cell lines, where it proved to be more active than in C2C12 skeletal myoblasts. Mirk mediated survival of the majority of clonogenic rhabdomyosarcoma cells. Knockdown of Mirk by RNA interference reduced the fraction of RD and of Rh30 rhabdomyosarcoma cells capable of colony formation 3- to 4-fold in multiple experiments. Depletion of Mirk induced cell death by apoptosis, as shown by increased numbers of terminal deoxynucleotidyl transferase-mediated nick-end labeling-positive cells and by increased binding of Annexin V. Mirk is a stress-activated kinase that mediates expression of contractile proteins in differentiating myoblasts, but Mirk is not essential for muscle formation in the embryo. It is likely that Mirk also facilitates survival of satellite cell-derived rhabdomyoblasts in regenerating skeletal muscle and aids their differentiation. This survival function is maintained in rhabdomyosarcoma, where Mirk may be a novel therapeutic target.

Original languageEnglish (US)
Pages (from-to)5143-5150
Number of pages8
JournalCancer Research
Volume66
Issue number10
DOIs
StatePublished - May 15 2006
Externally publishedYes

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Rhabdomyosarcoma
Cell Survival
Skeletal Myoblasts
Myoblasts
Phosphotransferases
Cell Line
Contractile Proteins
DNA Nucleotidylexotransferase
Annexin A5
Protein-Serine-Threonine Kinases
Growth
RNA Interference
Sarcoma
Neoplasms
Skeletal Muscle
Cell Death
Down-Regulation
Embryonic Structures
Maintenance
Apoptosis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mercer, S. E., Ewton, D. Z., Shah, S. M., Naqvi, A., & Friedman, E. (2006). Mirk/Dyrk1b mediates cell survival in rhabdomyosarcomas. Cancer Research, 66(10), 5143-5150. https://doi.org/10.1158/0008-5472.CAN-05-1539

Mirk/Dyrk1b mediates cell survival in rhabdomyosarcomas. / Mercer, Stephen E.; Ewton, Daina Z.; Shah, Sejal M; Naqvi, Asghar; Friedman, Eileen.

In: Cancer Research, Vol. 66, No. 10, 15.05.2006, p. 5143-5150.

Research output: Contribution to journalArticle

Mercer, SE, Ewton, DZ, Shah, SM, Naqvi, A & Friedman, E 2006, 'Mirk/Dyrk1b mediates cell survival in rhabdomyosarcomas', Cancer Research, vol. 66, no. 10, pp. 5143-5150. https://doi.org/10.1158/0008-5472.CAN-05-1539
Mercer SE, Ewton DZ, Shah SM, Naqvi A, Friedman E. Mirk/Dyrk1b mediates cell survival in rhabdomyosarcomas. Cancer Research. 2006 May 15;66(10):5143-5150. https://doi.org/10.1158/0008-5472.CAN-05-1539
Mercer, Stephen E. ; Ewton, Daina Z. ; Shah, Sejal M ; Naqvi, Asghar ; Friedman, Eileen. / Mirk/Dyrk1b mediates cell survival in rhabdomyosarcomas. In: Cancer Research. 2006 ; Vol. 66, No. 10. pp. 5143-5150.
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