title: Six1 mediates resistance to paclitaxel in breast cancer cells.
abstract: Paclitaxel resistance remains a major challenge in the treatment of breast cancer. Six1 is a homeodomain-containing transcription factor invloved in the initiation, progression and metastasis of breast cancer. We herein investigate the relationship between Six1 and resistance of paclitaxel in this study. The results indicate that six1 is a mediator of the paclitaxel resistance in breast cancer. The expression level of Six1 in breast cancer cells correlates with their resistance to paclitaxel. On the one hand, forced overexpression of Six1 in Six1-low/paclitaxel-sensitive MCF-7 or HS578T breast cancer cells induce their resistance to paclitaxel treatment directly; On the other hand, knockdown of endogenous Six1 in Six1-high/drug-resistant BT-474 breast cancer cells sensitized these cells to paclitaxel treatment. Besides, Six1 overexpression confers resistance to paclitaxel-mediated apoptosis in breast cancer cells. Furthermore, clinical data and the publicly available breast cancer gene expression datasets display that the association of Six1 expression with paclitaxel sensitivity is clinically relevant. In conclusion, these data suggest that Six1 may function as an important modifier of the paclitaxel response in breast cancer cells, and serve as a potential target for overcoming paclitaxel resistance in breast cancer.
authors.affiliation: Department of Oncology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, People's Republic of China. Electronic address: zhaomingli2013@163.com.
authors.forename: Zhaoming
authors.initials: Z
authors.lastname: Li
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhang
authors.forename: Feifei
authors.initials: F
authors.lastname: Nan
authors.forename: Yu
authors.initials: Y
authors.lastname: Chang
authors.forename: Feng
authors.initials: F
authors.lastname: Lv
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms; D019008:Drug Resistance, Neoplasm; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D017239:Paclitaxel / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; C099236:SIX1 protein, human; D017239:Paclitaxel
keywords: Apoptosis; Breast cancer; Paclitaxel resistance; Six1