Affiliations: [a] Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001, China | [b] Health Management Center, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, China | [c] Department of Radio-Oncology, Fudan university Shanghai Cancer Center, Shanghai 200433, China | [d] Department of Radio-Oncology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui 241001, China
Correspondence:
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Corresponding authors: Jundong Zhou, Suzhou Cancer Center Core Laboratory, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001, China. Yihong Chen, Department of Radio-Oncology, The First Affiliated Hospital of Wannan Medical College, 2# East Zheshan Road, Wuhu, Anhui 241001, China. Tel.: +86 13905535176; Fax: +86 553 5738279; E-mail: chenyihongf01@163.com.
Note: [1] These authors contributed equally to the study.
Abstract: BACKGROUND AND OBJECTIVE: Dysregulation of DNA polymerase iota (Pol ι) in breast cancer might contribute to the accumulation of genomic mutations and promotes breast cancer progression. In this study we explored the clinical relevance and biological function of Pol ι in breast cancer. METHODS: qRT-PCR was used to determine the expression levels of Pol ι in 31 breast cancer tissues. Then the stable overexpression of Pol ι and knockdown of Pol ι breast cancer cell lines were constructed. Wound-healing assay and transwell assay were performed to evaluate cell migratory and invasiveness, respectively. Signaling pathway was analyzed by western blot. RESULTS: The expression levels of Pol ι is overexpressed in breast cancer tissues and significantly higher in breast cancer tissues with lymph node metastasis compared to those without lymph node metastasis. Elevated Pol ι expression promoted migratory and invasiveness of breast cancer cells. Signaling pathway analysis indicated EGFR-ERK cascade works as a mediator of Pol ι-induced EMT of breast cancer cells. CONCLUSIONS: These data demonstrate the underlying mechanism by which Pol ι promotes breast cancer progression, suggesting that Pol ι may be a potential therapeutic target against breast cancer.
Keywords: Breast cancer, Pol ι, metastasis, EMT, EGFR
