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CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression
Author(s) -
Tsai HsiaoChi,
Chang AnChen,
Tsai ChunHao,
Huang YuanLi,
Gan Lijun,
Chen ChiKuan,
Liu ShihChia,
Huang TeYang,
Fong YiChin,
Tang ChihHsin
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27611
Subject(s) - abcg2 , osteosarcoma , gene knockdown , cancer research , doxorubicin , drug resistance , atp binding cassette transporter , cancer cell , chemistry , biology , pharmacology , cancer , apoptosis , transporter , biochemistry , chemotherapy , gene , microbiology and biotechnology , genetics
In recent years, osteosarcoma survival rates have failed to improve significantly with conventional treatment modalities because of the development of chemotherapeutic resistance. The human breast cancer resistance protein/ATP binding cassette subfamily G member 2 (BCRP/ABCG2), a member of the ATP‐binding cassette family, uses ATP hydrolysis to expel xenobiotics and chemotherapeutics from cells. CCN family member 2 (CCN2) is a secreted protein that modulates the biological function of cancer cells, enhanced ABCG2 protein expression and activation in this study via the α6β1 integrin receptor and increased osteosarcoma cell viability. CCN2 treatment downregulated miR‐519d expression, which promoted ABCG2 expression. In a mouse xenograft model, knockdown of CCN2 expression increased the therapeutic effect of doxorubicin, which was reversed by ABCG2 overexpression. Our data show that CCN2 increases ABCG2 expression and promotes drug resistance through the α6β1 integrin receptor, whereas CCN2 downregulates miR‐519d. CCN2 inhibition may represent a new therapeutic concept in osteosarcoma.