Annexin-I expression modulates drug resistance in tumor cells

Wang, Ying; Serfass, Lucile; Roy, Marie Odile; Wong, J; Bonneau, Anne Marie; Georges, Elias

doi:10.1016/j.bbrc.2003.12.117

Cited by 70 publications

(60 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Importantly, we observed a limited number of proteins that were differentially expressed in both paclitaxel-resistant cell models. These included tubulin β-5, annexin I, and GSTπ, that were overexpressed in the cytoplasmic fraction of the resistant cell lines and have been previously reported to have a role in paclitaxel resistance (6,20,21). PHB1, a protein not previously associated with taxane resistance, was consistently overexpressed in the microsomal fractions of both of the resistant cell lines.…”

Section: Phb1 Is Overexpressed In Microsomal Fractions Of Paclitaxel-mentioning

confidence: 85%

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Patel

Chatterjee

Vrbanac

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Paclitaxel has emerged as a front line treatment for aggressive malignancies of the breast, lung, and ovary. Successful therapy of cancer is frequently undermined by the development of paclitaxel resistance. There is a growing need to find other therapeutic targets to facilitate treatment of drug-resistant cancers. Using a proteomics approach, elevated levels of Prohibitin1 (PHB1) and GSTπ were found associated with paclitaxel resistance in discrete subcellular fractions of two drug-resistant sublines relative to their sensitive sublines. Immunofluorescence staining and fractionation studies revealed increased levels of PHB1 on the surface of resistant cell lines. Transiently silencing either PHB1 or GSTπ gene expression using siRNA in the paclitaxel-resistant cancer cell sublines partially sensitized these cells toward paclitaxel. Intriguingly, silencing PHB1 but not GSTπ resulted in activation of the intrinsic apoptosis pathway in response to paclitaxel. Similarly, stably silencing either PHB1 or GSTπ significantly improved paclitaxel sensitivity in A549TR cells both in vitro and in vivo. Our results indicate that PHB1 is a mediator of paclitaxel resistance and that this resistance may depend on the cellular localization of the protein. We suggest PHB1 as a potential target for therapeutic strategies for the treatment of drug-resistant tumors.apoptosis | glutathione-S-transferase Pi | mitochondria | plasma membrane | protein translocation

show abstract

Section: Phb1 Is Overexpressed In Microsomal Fractions Of Paclitaxel-mentioning

confidence: 85%

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Patel

Chatterjee

Vrbanac

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…3C, suppression of the ANXA1 expression resulted in a significant reduction of the cellular invasion ability, showing the strong malignant potential of ANXA1. In addition, MDA-MB-231 cells show a multidrug resistance due to upregulated ANXA1 expression (33,34). This cell line shows significant resistance to adriamycin, melphalan and etoposide compared to MCF-7 cells, which lack ANXA1 expression.…”

Section: Discussionmentioning

confidence: 97%

Upregulated Annexin A1 promotes cellular invasion in triple-negative breast cancer

et al. 2015

View full text Add to dashboard Cite

Abstract. Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein, involved in anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. While many studies have investigated the ANXA1 expression in various tumor types, the role of ANXA1 is not fully understood. Therefore, in the present study, we evaluated the ANXA1 expression in 211 breast cancer patients and compared the levels with clinicopathological factors. ANXA1 was positively expressed in 31 (14.7%) of the 211 cases in our cohort, and these positive cases were associated with triple-negative breast cancer (TNBC) (P=0.007) and venous invasion (P=0.028). The in vitro cell experiment found that the MDA-MB-231 cell line, which is a TNBC cell line, highly expressed ANXA1. Using this cell line, the functional role of ANXA1 in breast cancer was revealed and the knockdown of ANXA1 by specific siRNA demonstrated a significant reduction in cellular invasion. Further experiments indicated that ANXA1 was induced by hypoxia with hypoxia-inducible factor-1α induction. These results suggested that ANXA1, which enhanced breast cancer invasion and metastasis under hypoxia, were significantly associated with the worst patient outcome. This is particularly noted in TNBC, the group of breast cancer with the worst outcome for which new therapeutic implications are required. IntroductionBreast cancer is a leading cause of cancer related mortality among females worldwide and its incidence and mortality rate have been increasing throughout the recent years (1). The treatment of breast cancer has progressed over the past three decades with the development of the combination of chemotherapy, endocrine therapies and human epidermal growth factor receptor 2 (HER2)-targeted therapies (2-5). However, triple-negative breast cancer (TNBC), which is defined by the lack of the estrogen receptor (ER), the progesterone receptor (PgR) and HER2 expression, has not fully benefited from such advances in treatment. Therefore, patients with TNBCs are currently categorized as a sub group with the worst possible outcome. Although recent progress in gene sequencing technology has revealed the genetic profile of breast cancer including that of TNBC, the effort to understand breast cancer based on the diverse view from a more inclusive perspective is still needed (6-8).Annexin A1 (ANXA1) is a 37-kDa calcium-dependent phospholipid-linked protein belonging to the annexin superfamily and it is related to anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis (9-11). However, through those functions, ANXA1 is involved in tumorigenesis and the pivotal role of ANXA1 is not clearly understood. One of the main reasons for this is due to the fact that the functional role of ANXA1 in malignant tumors is quite different depending on the cancer type, such as head-and-neck, esophageal, gastric, colorectal, pancreatic, hepatic and prostate cancer (12-19). While ANXA1 is highly expressed in malignant tumors (20,21), some stu...

show abstract

“…AnxA1 expression has also been correlated with the development of metastasis in lung, breast, and head and neck squamous cell cancers (26,27,30). Although AnxA1 has been shown to modulate drug resistance in tumors and regulate cell proliferation, its association with the development of metastasis in some malignancies suggests that AnxA1 regulates the migration/invasion process (20,66). In our study, siRNA-mediated knockdown of AnxA1 expression resulted in a significant inhibition of SKCO-15 epithelial cell invasion demonstrating its role in regulating this process.…”

Section: Discussionmentioning

confidence: 99%

Annexin I Regulates SKCO-15 Cell Invasion by Signaling through Formyl Peptide Receptors

Babbin

Lee

Parkos

et al. 2006

Journal of Biological Chemistry

134

141

View full text Add to dashboard Cite

Annexin-I expression modulates drug resistance in tumor cells

Cited by 70 publications

References 32 publications

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Rescue of paclitaxel sensitivity by repression of Prohibitin1 in drug-resistant cancer cells

Upregulated Annexin A1 promotes cellular invasion in triple-negative breast cancer

Annexin I Regulates SKCO-15 Cell Invasion by Signaling through Formyl Peptide Receptors

Contact Info

Product

Resources

About