title: Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT.
abstract: Triple-negative breast cancer (TNBC) was regarded as the most aggressive and mortal subtype of breast cancer (BC) since the molecular subtype system has been established. Abundant studies have revealed that epithelial-mesenchymal transition (EMT) played a pivotal role during breast cancer metastasis and progression, especially in TNBC. Herein, we showed that inhibition the expression of replication factor C subunit 3 (RFC3) significantly attenuated TNBC metastasis and progression, which was associated with EMT signal pathway. In TNBC cells, knockdown of RFC3 can down-regulate mesenchymal markers and up-regulate epithelial markers, significantly attenuated cell proliferation, migration and invasion. Additionally, silencing RFC3 expression can decrease nude mice tumor volume, weight and relieve lung metastasis in vivo. Furthermore, we also demonstrated that overexpression of RFC3 in TNBC showed increased metastasis, progression and poor prognosis. We confirmed all of these results by immunohistochemistry analysis in 127 human TNBC tissues and found that RFC3 expression was significantly associated with poor prognosis in TNBC. Taken all these findings into consideration, we can conclude that up-regulation of RFC3 promotes TNBC progression through EMT signal pathway. Therefore, RFC3 could be an independent prognostic factor and therapeutic target for TNBC.
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: He
authors.affiliation: Department of Radiation Oncology, Xiamen Cancer Hospital, the First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen, 361003, Fujian, People's Republic of China.
authors.forename: San-Gang
authors.initials: SG
authors.lastname: Wu
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou, 510080, Guangdong, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Peng
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou, 510080, Guangdong, People's Republic of China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Road II, Guangzhou, 510080, Guangdong Province, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhenjiang Key Lab. of Radiation Oncology, 1 East Banshan Road, Hangzhou, 310022, People's Republic of China. Electronic address: chenming@zjcc.org.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China. Electronic address: baoyong0205@sina.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Bao