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HSP27 regulates viability and migration of cancer cell lines following irradiation
Benjamin Philipp Ernst1, Nadine Wiesmann1, Rita Gieringer1
1Department of Otorhinolaryngology, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
Abstract:
Despite improvements of radiotherapy and better outcomes of cancer patients resistances still limit the therapeutic success. The combined treatment of tumors by the use of irradiation as well as targeted therapies is a promising approach. By the use of a proteomic screening of lung and head and neck cancer cell lines we identified the heat shock protein HSP27 as a potential target protein for a combined treatment strategy. Overall expression of HSP27 was distinctly lower in HNSCCUM-02T cells which have a high HSP27 phosphorylation ratio, whereas A549 cells revealed the opposite. Irradiation and inhibition of HSP27 phosphorylation by MKII inhibition resulted in a significantly reduced viability in both cell lines. While irradiation impaired migration only in HNSCCUM-02T cells, MKII inhibition exerted that effect in both cell lines. In contrast, knockdown of HSP27 compromised the viability only in A549 cells. Additionally, MKII inhibition counteracts radiation-induced phosphorylation of HSP27 which causes an additive toxicity and reduced migratory capacity in HNSCCUM-02T when combined. Inhibition of HSP27 expression and phosphorylation in combination with radiotherapy may be an effective treatment option to overcome resistances.
Insights
Combining radiotherapy with targeted therapies, specifically inhibiting heat shock protein 27 (HSP27) phosphorylation, shows promise in overcoming cancer treatment resistance and reducing cell viability and migration.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy
Background:
- Cancer treatment resistance limits radiotherapy efficacy.
- Targeted therapies combined with irradiation present a promising strategy.
- Heat shock protein 27 (HSP27) is identified as a potential therapeutic target.
Purpose of the Study:
- To investigate the role of HSP27 in lung and head and neck cancer.
- To evaluate the combined effect of radiotherapy and HSP27 inhibition on cancer cells.
- To assess the impact on cell viability and migration.
Main Methods:
- Proteomic screening of lung and head and neck cancer cell lines.
- Treatment with irradiation and a heat shock protein 27 (HSP27) phosphorylation inhibitor (MKII).
- Assessment of cell viability, migration, and HSP27 phosphorylation levels.
- HSP27 knockdown experiments.
Main Results:
- Irradiation and MKII inhibition significantly reduced viability in both cell lines.
- MKII inhibition reduced migration in both cell lines, while irradiation only affected one.
- HSP27 knockdown compromised viability only in A549 cells.
- MKII inhibition counteracted radiation-induced HSP27 phosphorylation, leading to additive toxicity and reduced migration in HNSCCUM-02T cells.
Conclusions:
- Combined inhibition of HSP27 expression/phosphorylation with radiotherapy may overcome treatment resistance.
- Targeting HSP27 offers a potential strategy to enhance radiotherapy outcomes.
- Further research into HSP27 as a therapeutic target in combined cancer treatment is warranted.
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