Inhibition of EGFR nuclear shuttling decreases irradiation resistance in HeLa cells

Folia Histochemica Et Cytobiologica
Hong WeiLongtao Lu

Abstract

Cervical cancer is a leading cause of mortality in women worldwide. The resistance to irradiation at the advanced stage is the main reason for the poor prognosis and high mortality. This work aims to elucidate the molecular mechanism underlying the radio-resistance. In this study, we determined the pEGFR-T654 and pDNA-PK-T2609 expression level changes in irradiated HeLa cells treated with T654 peptide, a nuclear localization signal (NLS) inhibitor, to inhibit EGFR nuclear transport. Cell viability, cell cycle and migratory capacity were analyzed. Xenograft animal model was used to evaluate the effect of EGFR nuclear transport inhibition on the tumor growth in vivo. The enhanced translocation of nuclear EGFR in the irradiated HeLa cells correlated with the increasing level of pEGFR-T654 and pDNA-PK-T2609. Inhibition of EGFR nuclear translocation by NLS peptide inhibitor attenuated DNA damage repair in the irradiated HeLa cells, decreased cell viability and promoted cell death through arrest at G0 phase. NLS peptide inhibitor impaired the migratory capacity of irradiated HeLa cells, and negatively affected tumorigenesis in xenograft mice. This work puts forward a potential molecular mechanism of the irradiation resistance in cerv...Continue Reading

Citations

Feb 14, 2020·Cell Communication and Signaling : CCS·Abiola Abdulrahman AyanlajaDianshuai Gao
Jun 23, 2019·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Xuezhu RongEnhua Wang

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