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Polo-like kinase 1 (Plk1) in non-melanoma skin cancers
Travis L Schmit1, Weixiong Zhong, Minakshi Nihal
1Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA.
Abstract:
Polo-like kinase 1 (Plk1) is becoming an increasingly attractive target for cancer management. Plk1 has been shown to be overexpressed in a variety of cancers; however its role in skin cancers is not well-understood. We recently demonstrated that Plk1 is overexpressed in human melanoma and gene-knockdown as well as chemical-inhibition of Plk1 resulted in a significant decrease in melanoma cell viability and growth without affecting the growth of the normal human epidermal melanocytes (NHEMs). Further, the observed anti-proliferative response of Plk1 was found to be accompanied with a significant G(2)/M cell cycle arrest, mitotic catastrophe and induction of apoptosis in melanoma cells. In this study, we determined the expression profile of Plk1 in non-melanoma skin cancers viz. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Our data demonstrated that like melanoma, Plk1 is significantly overexpressed in BCC and SCC samples. Further, we also found that compared to normal human epidermal keratinocytes (NHEKs), Plk1 was overexpressed at both the protein and mRNA levels in squamous A253 and A431 cells. In addition, a similar protein expression pattern was found for the downstream targets of Plk1, viz. Cdk1, Cyclin B1 and Cdc25C. We believe that the expression pattern of Plk1 in the various skin cancers, the observed insusceptibility of normal cells to Plk1 inhibition and the easy accessibility for topical applications lends the skin as an attractive tissue for Plk1 based cancer chemoprevention and chemotherapeutic applications.
Insights
Polo-like kinase 1 (Plk1) is overexpressed in skin cancers like melanoma, basal cell carcinoma, and squamous cell carcinoma. Inhibiting Plk1 reduces cancer cell growth without harming normal cells, suggesting Plk1 as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Polo-like kinase 1 (Plk1) is a key regulator of cell division and is implicated in various cancers.
- The role of Plk1 in non-melanoma skin cancers, such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression profile of Plk1 in BCC and SCC.
- To evaluate the therapeutic potential of Plk1 inhibition in skin cancers.
Main Methods:
- Quantitative analysis of Plk1 expression in human skin cancer tissues (BCC, SCC) and cell lines.
- Assessment of Plk1 inhibition effects on cell viability, proliferation, cell cycle, and apoptosis in melanoma and keratinocyte cell lines.
- Analysis of downstream Plk1 targets, including Cdk1, Cyclin B1, and Cdc25C.
Main Results:
- Plk1 is significantly overexpressed in BCC and SCC samples compared to normal skin.
- Plk1 inhibition reduced melanoma cell viability and growth, inducing G2/M cell cycle arrest, mitotic catastrophe, and apoptosis.
- Normal human epidermal melanocytes (NHEMs) and keratinocytes (NHEKs) showed insusceptibility to Plk1 inhibition.
- Downstream targets of Plk1 (Cdk1, Cyclin B1, Cdc25C) showed similar overexpression patterns in cancer cells.
Conclusions:
- Plk1 is a promising therapeutic target for various skin cancers, including melanoma, BCC, and SCC.
- The selective toxicity of Plk1 inhibition towards cancer cells and the accessibility of skin for topical application support its chemopreventive and chemotherapeutic potential.
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