Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 234, Issue 6, Pages 9297-9307Publisher
WILEY
DOI: 10.1002/jcp.27611
Keywords
ABCG2; CCN2; chemotherapeutic resistance; osteosarcoma
Categories
Funding
- Taiwan's Ministry of Science and Technology [MOST 107-2320-B-039-019-MY3, MOST 107-2314-B-039-014-]
- China Medical University [CMU 107-ASIA-09]
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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 alpha 6 beta 1 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 alpha 6 beta 1 integrin receptor, whereas CCN2 downregulates miR-519d. CCN2 inhibition may represent a new therapeutic concept in osteosarcoma.
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