title: Chemoresistance is associated with overexpression of HAX-1, inhibition of which resensitizes drug-resistant breast cancer cells to chemotherapy.
abstract: Acquired resistance to standard chemotherapy is the common and critical limitation for cancer therapy. Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) has been reported to be upregulated in numerous cancers. However, the role of HAX-1 in oncotherapy remains unclear. In this study, we established MDA-MB-231 cell lines which were resistant to cisplatin (MDA-MB-231/CR) or doxorubicin (MDA-MB-231/DR) to study the chemoresistance in breast cancer. As a result, the HAX-1 which is an apoptosis-associated protein was observed to be overexpressed in both MDA-MB-231/CR and MDA-MB-231/DR compared with the routine MDA-MB-231 cells. Moreover, knockdown of HAX-1 via RNA interference decreased IC50 level of cisplatin by 70.91% in MDA-MB-231/CR cells, and the IC50 level of doxorubicin was decreased by 76.46% in MDA-MB-231/DR cells when the HAX-1 was downregulated. Additionally, we found that the knockdown of HAX-1 induced the release of cytochrome C from mitochondria, resulting in the activation of caspases. Taken together, our study indicates that the overexpression of HAX-1 is essential in the development of chemoresistance in breast cancer. Furthermore, we identify that HAX-1 may become the target for cancer therapy.
authors.affiliation: 1 Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1 Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: 2 Oncology Department, Zhejiang Provincial People's Hospital, Hangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1 Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Liqian
authors.initials: L
authors.lastname: Xu
authors.affiliation: 1 Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: 1 Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C104759:HAX1 protein, human; D034741:RNA, Small Interfering; D004317:Doxorubicin; D002945:Cisplatin; D005472:Fluorouracil
keywords: HAX-1; apoptosis; breast cancer; chemoresistance; chemotherapeutics