Targeted depletion of polo-like kinase (Plk) 1 through lentiviral shrna or a small-molecule inhibitor causes mitotic catastrophe and induction of apoptosis in human melanoma cells

Travis L. Schmit, Weixiong Zhong, Vijayasaradhi Setaluri, Vladimir S. Spiegelman, Nihal Ahmad

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Melanoma, one of the most lethal forms of skin cancer, remains resistant to currently available treatments. Therefore, additional target-based approaches are needed for the management of this neoplasm. Polo-like kinase 1 (Plk1) has been shown to be a crucial regulator of mitotic entry, progression, and exit. Elevated Plk1 level has been associated with aggressiveness of several cancer types and with poor disease prognosis. However, the role of Plk1 in melanoma is not well established. Here, we show that Plk1 is overexpressed in both clinical tissue specimens and cultured human melanoma cells (WM115, A375, and HS294T) when compared with normal skin tissues and cultured normal melanocytes, respectively. Furthermore, Plk1 gene knockdown through Plk1-specific shRNA or its activity inhibition by a small-molecule inhibitor resulted in a significant decrease in the viability and growth of melanoma cells without affecting normal human melanocytes. In addition, Plk1 inhibition resulted in a significant (i) decrease in clonogenic survival, (ii) multiple mitotic errors, (iii) G 2/M cell-cycle arrest, and (iv) apoptosis of melanoma cells. This study suggests that Plk1 may have a functional relevance toward melanoma development and/or progression. We suggest that the targeting of Plk1 may be a viable approach for the treatment of melanoma.

Original languageEnglish (US)
Pages (from-to)2843-2853
Number of pages11
JournalJournal of Investigative Dermatology
Volume129
Issue number12
DOIs
StatePublished - Jun 26 2009

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Melanoma
Apoptosis
Molecules
Melanocytes
Skin
Tissue
Gene Knockdown Techniques
polo-like kinase 1
Skin Neoplasms
Cell Cycle Checkpoints
Small Interfering RNA
Neoplasms
Genes
Cells
Survival
Growth

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

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title = "Targeted depletion of polo-like kinase (Plk) 1 through lentiviral shrna or a small-molecule inhibitor causes mitotic catastrophe and induction of apoptosis in human melanoma cells",
abstract = "Melanoma, one of the most lethal forms of skin cancer, remains resistant to currently available treatments. Therefore, additional target-based approaches are needed for the management of this neoplasm. Polo-like kinase 1 (Plk1) has been shown to be a crucial regulator of mitotic entry, progression, and exit. Elevated Plk1 level has been associated with aggressiveness of several cancer types and with poor disease prognosis. However, the role of Plk1 in melanoma is not well established. Here, we show that Plk1 is overexpressed in both clinical tissue specimens and cultured human melanoma cells (WM115, A375, and HS294T) when compared with normal skin tissues and cultured normal melanocytes, respectively. Furthermore, Plk1 gene knockdown through Plk1-specific shRNA or its activity inhibition by a small-molecule inhibitor resulted in a significant decrease in the viability and growth of melanoma cells without affecting normal human melanocytes. In addition, Plk1 inhibition resulted in a significant (i) decrease in clonogenic survival, (ii) multiple mitotic errors, (iii) G 2/M cell-cycle arrest, and (iv) apoptosis of melanoma cells. This study suggests that Plk1 may have a functional relevance toward melanoma development and/or progression. We suggest that the targeting of Plk1 may be a viable approach for the treatment of melanoma.",
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Targeted depletion of polo-like kinase (Plk) 1 through lentiviral shrna or a small-molecule inhibitor causes mitotic catastrophe and induction of apoptosis in human melanoma cells. / Schmit, Travis L.; Zhong, Weixiong; Setaluri, Vijayasaradhi; Spiegelman, Vladimir S.; Ahmad, Nihal.

In: Journal of Investigative Dermatology, Vol. 129, No. 12, 26.06.2009, p. 2843-2853.

Research output: Contribution to journalArticle

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T1 - Targeted depletion of polo-like kinase (Plk) 1 through lentiviral shrna or a small-molecule inhibitor causes mitotic catastrophe and induction of apoptosis in human melanoma cells

AU - Schmit, Travis L.

AU - Zhong, Weixiong

AU - Setaluri, Vijayasaradhi

AU - Spiegelman, Vladimir S.

AU - Ahmad, Nihal

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