TY - GEN
T1 - Molecular interactions of polo-like kinase 1 (PLK1) in colorectal cancer
AU - Ng, W. T. W.
AU - Shin, J.
AU - Yang, T.
AU - Roberts, T.
AU - Wang, B.
AU - Begg, J.
AU - Lee, C. S.
PY - 2016
Y1 - 2016
N2 - ![CDATA[Radiotherapy (RT) improves the local control of rectal cancer but patient responses to RT are variable. Biomarkers are needed to determine the radiosensitivity of these tumours. Microsatellite instability (MSI) accounts for 15% of colorectal cancer (CRC) cases and the associated proteins were shown to be involved in DNA damage responses (DDR). PLK1 promotes cell cycle progression and is also involved in recovery from DNA damage. Deregulation of PLK1 causes genetic instability due to G2-M checkpoint escape. PLK1 overexpression is associated with poor tumour prognosis. This study investigated the interactions between PLK1, MSI and ionising irradiation (IR) and explored the molecular mechanisms that are associated to PLK1 deregulation in CRC. siRNA was used to deplete PLK1. The effects of the knockdown and IR were then analysed by real-time quantitative PCR, western blot, cell survival assays, caspase 3/7 assay, annexin V binding assay and cell cycle analysis. Sanger sequencing was performed to detect mutations in PLK1 gene. In MSI high cells (HCT116, SW48), PLK1 expression decreased post-IR whereas it remained unaffected in microsatellite stable (MSS) cells (Colo320DM, T84). MSI high cells were more radiosensitive than the MSS cells. PLK1 reduction resulted in substantial reduction of cell survival, as well as increased induction of apoptosis and G2/M blockage in Colo320DM, HCT116 and SW48 cells but not T84 cells. These effects were additive in the responsive cells when the treatment was combined with IR. PLK1 sequencing studies showed that only secondary mutations were detected at the silencer region of PLK1 in HCT116 and SW48. In conclusion, MSI has an impact on PLK1 expression which in turns affects the cell survival after IR. Moreover, PLK1 knockdown additionally improved the effects of IR in some of the CRC cells, including some radio resistant cells. Lastly, sequencing concluded that mutation did not play a major role in PLK1 expression level in CRC.]]
AB - ![CDATA[Radiotherapy (RT) improves the local control of rectal cancer but patient responses to RT are variable. Biomarkers are needed to determine the radiosensitivity of these tumours. Microsatellite instability (MSI) accounts for 15% of colorectal cancer (CRC) cases and the associated proteins were shown to be involved in DNA damage responses (DDR). PLK1 promotes cell cycle progression and is also involved in recovery from DNA damage. Deregulation of PLK1 causes genetic instability due to G2-M checkpoint escape. PLK1 overexpression is associated with poor tumour prognosis. This study investigated the interactions between PLK1, MSI and ionising irradiation (IR) and explored the molecular mechanisms that are associated to PLK1 deregulation in CRC. siRNA was used to deplete PLK1. The effects of the knockdown and IR were then analysed by real-time quantitative PCR, western blot, cell survival assays, caspase 3/7 assay, annexin V binding assay and cell cycle analysis. Sanger sequencing was performed to detect mutations in PLK1 gene. In MSI high cells (HCT116, SW48), PLK1 expression decreased post-IR whereas it remained unaffected in microsatellite stable (MSS) cells (Colo320DM, T84). MSI high cells were more radiosensitive than the MSS cells. PLK1 reduction resulted in substantial reduction of cell survival, as well as increased induction of apoptosis and G2/M blockage in Colo320DM, HCT116 and SW48 cells but not T84 cells. These effects were additive in the responsive cells when the treatment was combined with IR. PLK1 sequencing studies showed that only secondary mutations were detected at the silencer region of PLK1 in HCT116 and SW48. In conclusion, MSI has an impact on PLK1 expression which in turns affects the cell survival after IR. Moreover, PLK1 knockdown additionally improved the effects of IR in some of the CRC cells, including some radio resistant cells. Lastly, sequencing concluded that mutation did not play a major role in PLK1 expression level in CRC.]]
KW - colorectal cancer
KW - biochemical markers
KW - radiotherapy
UR - http://handle.uws.edu.au:8081/1959.7/uws:36217
UR - http://www.pathsoc.org/files/meetings/2016WinterMtg/2016WMLondonPrelim.pdf
U2 - 10.1002/path.4705
DO - 10.1002/path.4705
M3 - Conference Paper
SP - S6-S6
BT - Winter Meeting: Abstracts of the 205th Meeting of the Pathological Society of Great Britain & Ireland, 7-8 January 2016, Guoman Tower Hotel, London
PB - Pathological Society
T2 - Pathological Society of Great Britain and Ireland. Meeting
Y2 - 7 January 2016
ER -
