title: The pro-adhesive and pro-survival effects of glucocorticoid in human ovarian cancer cells.
abstract: 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 β1, α4, and α5 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 β1. 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.
authors.affiliation: Department of PathophysiologyThe Second Military Medical University, Shanghai, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Obstetrics and GynecologyChanghai Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of PathophysiologyThe Second Military Medical University, Shanghai, China.
authors.forename: Xinglei
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of PathophysiologyThe Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of PathophysiologyThe Second Military Medical University, Shanghai, China.
authors.forename: Gaoxiang
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of PathophysiologyThe Second Military Medical University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Obstetrics and GynecologyChanghai Hospital, The Second Military Medical University, Shanghai, China lujian326@163.com huning324@aliyun.com.
authors.forename: Ning
authors.initials: N
authors.lastname: Hui
authors.affiliation: Department of PathophysiologyThe Second Military Medical University, Shanghai, China lujian326@163.com huning324@aliyun.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D015415:Biomarkers; D002448:Cell Adhesion / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D018396:Mucin-1 / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; C497483:CD44 protein, human; D005353:Fibronectins; D005938:Glucocorticoids; D018960:Hyaluronan Receptors; D007797:Laminin; D018396:Mucin-1; D003907:Dexamethasone; D003094:Collagen; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; cell adhesion; cell survival; dexamethasone; fibronectin; mucin 1