Journal
JOURNAL OF MOLECULAR ENDOCRINOLOGY
Volume 57, Issue 1, Pages 61-72Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-15-0142
Keywords
dexamethasone; cell adhesion; fibronectin; mucin 1; Akt; cell survival
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Funding
- National Natural Science Foundation of China [81472690, 91029722]
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Cell adhesion to extracellular matrix ( ECM) is controlled by multiple signaling molecules and intracellular pathways, and is pivotal for survival and growth of cells from most solid tumors. Our previous works demonstrated that dexamethasone ( DEX) significantly enhances cell adhesion and cell resistance to chemotherapeutics by increasing the levels of integrin beta 1, alpha 4, and alpha 5 in human ovarian cancer cells. However, it is unclear whether the components of ECM or other membrane molecules are also involved in the pro-adhesive effect of DEX in ovarian cancer cells. In this study, we demonstrated that the treatment of cells with DEX did not change the expression of collagens ( I, III, and IV), laminin, CD44, and its principal ligand hyaluronan ( HA), but significantly increased the levels of intracellular and secreted fibronectin ( FN). Inhibiting the expression of FN with FN1 siRNA or blocking CD44, another FN receptor, with CD44 blocking antibody significantly attenuated the pro-adhesion of DEX, indicating that upregulation of FN mediates the pro-adhesive effect of DEX by its interaction with CD44 besides integrin beta 1. Moreover, DEX significantly enhanced cell resistance to the chemotherapeutic agent paclitaxel ( PTX) by activating PI-3K-Akt pathway. Finally, we found that DEX also significantly upregulated the expression of MUC1, a transmembrane glycoprotein. Inhibiting the expression of MUC1 with MUC1 siRNA significantly attenuated the DEX-induced effects of pro-adhesion, Akt-activation, and pro-survival. In conclusion, these results provide new data that upregulation of FN and MUC1 by DEX contributes to DEX-induced pro-adhesion and protects ovarian cancer cells from chemotherapy.
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