Abstract
In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression.
| Original language | English |
|---|---|
| Pages (from-to) | 25076-25092 |
| Number of pages | 17 |
| Journal | Oncotarget |
| Volume | 6 |
| Issue number | 28 |
| DOIs | |
| Publication status | Published - 2015 |
Fingerprint
Keywords
- Annexin A1
- Cancer stem cells
- Cell invasion
- EMT
- Prostate cancer
ASJC Scopus subject areas
- Oncology
Cite this
Annexin A1 is involved in the acquisition and maintenance of a stem cell-like/aggressive phenotype in prostate cancer cells with acquired resistance to zoledronic acid. / Bizzarro, Valentina; Belvedere, Raffaella; Milone, Maria Rita; Pucci, Biagio; Lombardi, Rita; Bruzzese, Francesca; Popolo, Ada; Parente, Luca; Budillon, Alfredo; Petrella, Antonello.
In: Oncotarget, Vol. 6, No. 28, 2015, p. 25076-25092.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Annexin A1 is involved in the acquisition and maintenance of a stem cell-like/aggressive phenotype in prostate cancer cells with acquired resistance to zoledronic acid
AU - Bizzarro, Valentina
AU - Belvedere, Raffaella
AU - Milone, Maria Rita
AU - Pucci, Biagio
AU - Lombardi, Rita
AU - Bruzzese, Francesca
AU - Popolo, Ada
AU - Parente, Luca
AU - Budillon, Alfredo
AU - Petrella, Antonello
PY - 2015
Y1 - 2015
N2 - In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression.
AB - In this study, we have characterized the role of annexin A1 (ANXA1) in the acquisition and maintenance of stem-like/aggressive features in prostate cancer (PCa) cells comparing zoledronic acid (ZA)-resistant DU145R80 with their parental DU145 cells. ANXA1 is over-expressed in DU145R80 cells and its down-regulation abolishes their resistance to ZA. Moreover, ANXA1 induces DU145 and DU145R80 invasiveness acting through formyl peptide receptors (FPRs). Also, ANXA1 knockdown is able to inhibit epithelial to mesenchymal transition (EMT) and to reduce focal adhesion kinase (FAK) and metalloproteases (MMP)-2/9 expression in PCa cells. DU145R80 show a cancer stem cell (CSC)-like signature with a high expression of CSC markers including CD44, CD133, NANOG, Snail, Oct4 and ALDH7A1 and CSC-related genes as STAT3. Interestingly, ANXA1 knockdown induces these cells to revert from a putative prostate CSC to a more differentiated phenotype resembling DU145 PCa cell signature. Similar results are obtained concerning some drug resistance-related genes such as ATP Binding Cassette G2 (ABCG2) and Lung Resistant Protein (LRP). Our study provides new insights on the role of ANXA1 protein in PCa onset and progression.
KW - Annexin A1
KW - Cancer stem cells
KW - Cell invasion
KW - EMT
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=84944463645&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84944463645&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.4725
DO - 10.18632/oncotarget.4725
M3 - Article
C2 - 26312765
AN - SCOPUS:84944463645
VL - 6
SP - 25076
EP - 25092
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 28
ER -