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

doi:10.18632/oncotarget.4725

Cited by 53 publications

(55 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…7 The role of this protein in PCa development and progression is still debated, however we have recently showed that the protein plays a significant part in regulating aggressive behaviors of a chemoresistant sub-line of DU145 PCa cells. 9 In the present study, we demonstrated that ANXA1 is able to mediate some of the pro-oncogenic hypoxia-related events in vitro.…”

Section: Discussionsupporting

confidence: 58%

“…31,32 and that the occurrence of this event in cancer cells possibly will result in the acquisition of a very aggressive phenotype characterized by the acquisition of augmented invasion capability and of stem-cell like features. 9 Therefore, we evaluated if ANXA1 could have a proinvasive role in LNCaP, DU145 and PC3 cell lines thanks to its ability to activate FPRs, as previously reported in pancreas and colon carcinomas. 18,33 We performed a matrigel invasion assay by stimulating or not LNCaP, DU145 and PC3 cells by administration of Ac2-26 peptide, the N-terminus mimetic peptide of ANXA1, of the natural FPR agonist N-FormylmethionyL-leucyL-phenylalanine (fMLP) peptide 30 and of 2 FPR antagonists, in normoxia and hypoxia conditions.…”

Section: Secretion Of Anxa1 Protein Has a Crucial Role During Hypoxiamentioning

confidence: 95%

“…18,9 Hence, we analyzed sub-cellular protein expression by Western blotting. In particular, we obtained membrane, cytosol and supernatant protein extracts as described in Materials and Methods section.…”

Section: Anxa1 Expression and Localization In Pca Cell Linesmentioning

confidence: 99%

“…This protein is involved in a wide range of physio-pathological processes, including cancer development. 8,9,10 ANXA1 dysregulation in PCa has been reported by numerous studies with controversial results. It has been shown that overall ANXA1 expression is unaffected 11,12 or downregulated in in situ PCa 13,2 whereas cancer microarray databases from Oncomine (publicly available at http://www.oncomine.org) show an increase of the protein expression in the more metastatic PCa stages.…”

Section: Introductionmentioning

confidence: 99%

“…14,15 We have previously demonstrated that ANXA1 is able to confer and maintain a more aggressive phenotype in chemo-resistant PCa cells. 9 Here we have investigated the mechanism(s) by which ANXA1 promotes PCa progression, utilizing a well characterized in vitro experimental model of cancer development based on the comparison of the 3 human LNCaP, DU145 and PC3 PCa cells. These cell lines differ in their phenotypes and malignancy levels and reflect the androgenindependent progression of PCa: more interestingly, they show dissimilar expression profiles of ANXA1 protein.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Hypoxia regulates ANXA1 expression to support prostate cancer cell invasion and aggressiveness

Bizzarro

Belvedere

Migliaro

et al. 2016

Cell Adhesion & Migration

Self Cite

View full text Add to dashboard Cite

Annexin A1 (ANXA1) is a Ca 2C -binding protein overexpressed in the invasive stages of prostate cancer (PCa) development; however, its role in this tumor metastatization is largely unknown. Moreover, hypoxic conditions in solid tumors have been related to poor prognosis in PCa patients. We have previously demonstrated that ANXA1 is implicated in the acquisition of chemo-resistant features in DU145 PCa cells conferring them a mesenchymal/metastatic phenotype. In this study, we have investigated the mechanisms by which ANXA1 regulates metastatic behavior in LNCaP, DU145 and PC3 cells exposed to hypoxia. ANXA1 was differentially expressed by PCa cell lines in normoxia whereas hypoxic stimuli resulted in a significant increase of protein expression. Additionally, in low oxygen conditions ANXA1 was extensively secreted out-side the cells where its binding to formyl peptide receptors (FPRs) induced cell invasion. Loss and gain of function experiments performed by using the RNA interfering siANXA1 and an ANXA1 over-expressing plasmid (MF-ANXA1), also confirmed the leading role of the protein in modulating LNCaP, DU145 and PC3 cell invasiveness. Finally, ANXA1 played a crucial role in the regulation of cytoskeletal dynamics underlying metastatization process, such as the loss of adhesion molecules and the occurrence of the epithelial to mesenchymal transition (EMT). ANXA1 expression increased inversely to epithelial markers such as E-cadherin and cytokeratins 8 and 18 (CKs) and proportionally to mesenchymal ones such as vimentin, ezrin and moesin. Our results indicated that ANXA1 may be a key mediator of hypoxia-related metastasis-associated processes in PCa.

show abstract

Section: Discussionsupporting

confidence: 58%

Section: Secretion Of Anxa1 Protein Has a Crucial Role During Hypoxiamentioning

confidence: 95%

Section: Anxa1 Expression and Localization In Pca Cell Linesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hypoxia regulates ANXA1 expression to support prostate cancer cell invasion and aggressiveness

Bizzarro

Belvedere

Migliaro

et al. 2016

Cell Adhesion & Migration

Self Cite

View full text Add to dashboard Cite

show abstract

Sonic hedgehog signaling is associated with resistance to zoledronic acid in CD133high/CD44high prostate cancer stem cells

et al. 2021

View full text Add to dashboard Cite

Upregulation of annexin A1 expression by butyrate in human melanoma cells induces invasion by inhibiting E-cadherin expression

et al. 2016

View full text Add to dashboard Cite

Epithelial to mesenchymal transition (EMT) is a critical step in the metastasis of epithelial cancer cells. Butyrate, which is produced from dietary fiber by colonic bacterial fermentation, has been reported to influence EMT. However, some studies have reported that butyrate promotes EMT, while others have reported an inhibitory effect. To clarify these controversial results, it is necessary to elucidate the mechanism by which butyrate can influence EMT. In this study, we examined the potential role of annexin A1 (ANXA1), which was previously reported to promote EMT in breast cancer cells, as a mediator of EMT regulation by butyrate. We found that ANXA1 mRNA and protein were expressed in highly invasive melanoma cell lines (A2058 and A375), but not in SK-MEL-5 cells, which are less invasive. We also showed that butyrate induced ANXA1 mRNA and protein expression and promoted EMT-related cell invasion in SK-MEL-5 cells. Downregulation of ANXA1 expression using specific small interfering RNAs in butyrate-treated SK-MEL-5 cells resulted in increased expression of the epithelial marker E-cadherin and decreased cell invasion. Moreover, overexpressing ANXA1 decreased the expression of the E-cadherin. Collectively, these results indicate that butyrate induces the expression of ANXA1 in human melanoma cells, which then promotes invasion through activating the EMT signaling pathway.

show abstract

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

Abstract: ABSTRACT

Cited by 53 publications

References 99 publications

Hypoxia regulates ANXA1 expression to support prostate cancer cell invasion and aggressiveness

Hypoxia regulates ANXA1 expression to support prostate cancer cell invasion and aggressiveness

Sonic hedgehog signaling is associated with resistance to zoledronic acid in CD133high/CD44high prostate cancer stem cells

Upregulation of annexin A1 expression by butyrate in human melanoma cells induces invasion by inhibiting E-cadherin expression

Contact Info

Product

Resources

About