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.
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.
Schmit
Travis L
TL
Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53706, USA.
Zhong
Weixiong
W
Setaluri
Vijayasaradhi
V
Spiegelman
Vladimir S
VS
Ahmad
Nihal
N
D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007668:Kidney / Q000166:cytology; D016086:Lentivirus / Q000235:genetics; D008545:Melanoma / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D008938:Mitosis / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D012879:Skin Physiological Phenomena; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1