[논문]KDM3A regulates Slug expression to promote the invasion of MCF7 breast cancer cells in hypoxia

Ahn, Hyun-Jung; Moon, Byul; Park, Mijin; Kim, Jung-Ae

doi:10.3892/ol.2020.12199

[해외논문] KDM3A regulates Slug expression to promote the invasion of MCF7 breast cancer cells in hypoxia 원문보기

Oncology letters, v.20 no.6, 2020년, pp.335 -

Ahn, Hyun-Jung (Personalized Genomic Medicine Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea) , Moon, Byul (Personalized Genomic Medicine Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea) , Park, Mijin (Personalized Genomic Medicine Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea) , Kim, Jung-Ae (Personalized Genomic Medicine Research Centre, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea)

Abstract ▼ AI-Helper

Oxygen deprivation (hypoxia), which frequently occurs in the tumour microenvironment, is a strong driver of the phenotypic transition of cancer cells. An increase in metastatic potential such as cell invasion is a well-known phenotypical change induced in hypoxia. The present study demonstrated that lysine demethylase 3A (KDM3A), a Jumonji C domain-containing KDM, is involved in the hypoxia-induced invasion of MCF7 breast cancer cells. KDM3A depletion inhibits the induction of cell invasion without affecting MCF7 cell survival rate or proliferation under hypoxic conditions, whereas KDM3A overexpression enhances MCF7 cell invasion even under normoxic conditions. KDM3A suppresses E-cadherin expression, which is associated with epithelial-to-mesenchymal transition (EMT)-mediated cell invasion in hypoxia. In addition, KDM3A promotes the expression of Slug, an EMT transcription factor that negatively regulates E-cadherin expression. Consistent with this finding, the removal of the repressive transcription marker, dimethylated histone H3 at lysine 9 from the Slug promoter is dependent on hypoxia-induced recruitment of KDM3A. Collectively, the results of the present study suggest that KDM3A is a crucial transcriptional coactivator of Slug expression to induce MCF7 breast cancer cell invasion in hypoxia, and that inhibition of KDM3A may efficaciously prevent metastatic cancer development.

Keyword

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