Up-regulated Annexin A1 expression in gastrointestinal cancer is associated with cancer invasion and lymph node metastasis

Sato, Yu; Kumamoto, Kensuke; Saito, Katsuharu; Okayama, Hirokazu; Hayase, Suguru; Kofunato, Yasuhide; Miyamoto, Koutaro; Nakamura, Izumi; Ohki, Shinji; Koyama, Yoshihisa; Takenoshita, Seiichi

doi:10.3892/etm.2011.210

Cited by 41 publications

(60 citation statements)

References 23 publications

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“…While the ANXA1 expression on cancer tissues is downregulated in head and neck, esophageal and prostate cancer, the expression is upregulated in stomach, colorectal, pancreas and hepatic cancer (12)(13)(14)(15)(16)(17)(18)(19). In breast cancer, the expression and functional roles of ANXA1 are controversial.…”

Section: Discussionmentioning

confidence: 99%

“…Another study reported that ANXA1 may promote metastasis formation by enhancing the TGFβ/Smad signaling pathway (27). On the other hand, we previously reported that the expression of ANXA1 is upregulated in gastric and colon cancer and it is involved in cancer invasion as well as lymph node metastasis (16). Here, we investigated the ANXA1 expression in breast cancer and the relationship between ANXA1 expression and clinicopathological features.…”

Section: Introductionmentioning

confidence: 99%

“…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)(13)(14)(15)(16)(17)(18)(19). While ANXA1 is highly expressed in malignant tumors (20,21), some studies have demonstrated that lower expression of ANXA1 is associated with poor prognosis (22) and cancer progression (23)(24)(25) in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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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...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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“…ANXA1 also exhibits a low expression in GC and negatively correlates with invasion and metastasis [4] . However, other studies have revealed opposite results [5,6] . We performed laser capture microdissection (LCM) to investigate the relation of ANXA1 expression in GC to the clinical parameters and to obtain purified gastric adenocarcinoma cells (GAC) and normal gastric epithelial cells (NGEC).…”

Section: Introductionmentioning

confidence: 86%

Identification of Annexin A1 protein expression in human gastric adenocarcinoma using proteomics and tissue microarray

Zhang

Li²,

Liu³

et al. 2013

WJG

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AIM:To study the differential expression of Annexin A1 (ANXA1) protein in human gastric adenocarcinoma. This study was also designed to analyze the relationship between ANXA1 expression and the clinicopathological parameters of gastric carcinoma. O after trypsin digestion. Differential protein expressions were quantitatively identified between GAC and NGEC by nanoliter-reverse-phase liquid chromatography-mass/mass spectrometry (nano-RPLC-MS/MS). The expressions of ANXA1 in GAC and NGEC were verified by western blot analysis. The tissue microarray containing the expressed ANXA1 in 75 pairs of gastric carcinoma and paracarcinoma specimens was detected by immunohistochemistry (IHC). The relationship between ANXA1 expression and clinicopathological parametes of gastric carcinoma was analyzed. METHODS: RESULTS:A total of 78 differential proteins were identified. Western blotting revealed that ANXA1 expression was significantly upregulated in GAC (2.17/1, P < 0.01).IHC results showed the correlations between ANXA1 protein expression and the clinicopathological parameters, including invasive depth (T stage), lymph node metastasis (N stage), distant metastasis (M stage) and tumour-lymph node metastasis stage (P < 0.01). However, the correlations between ANXA1 protein expression and the remaining clinicopathological parameters, including sex, age, histological differentiation and the size of tumour were not found (P > 0.05). CONCLUSION:The upregulated ANXA1 expression may be associated with carcinogenesis, progression, invasion and metastasis of GAC. This protein could be considered as a biomarker of clinical prognostic prediction and targeted therapy of GAC.

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“…We also reported that ANXA1 enhanced breast cancer invasion and metastasis under hypoxia in in vitro cell experiments, indicating that ANXA1 was apparently associated with breast cancer progression 4) . In addition, we stated that colon cancer cases with positive ANXA1 expression by IHC staining were associated with lymphatic invasion (P = 0.011), venous invasion (P = 0.023), and lymph node metastasis (P = 0.042) 5) . The colon cancer cases with positive ANXA1 staining were not statistically associated with poor survival 5) .…”

Section: Introductionmentioning

confidence: 95%

Annexin A1 is upregulated in p53-positive gastric cancer

Saito

Nakano

Kikuchi

et al. 2018

Ann. Cancer Res. Therap.

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Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein that is associated with anti-inflammatory effects, regulation of cellular differentiation, proliferation, and apoptosis. In gastric cancer, ANXA1 is upregulated and has a significant role of gastric tumorigenesis. Although ANXA1 is known to be a p53 target gene, the association between ANXA1 expression and p53 expression is yet to be fully investigated in gastric cancer. We therefore investigated in this study the expressions of ANXA1 and p53 by immunohistochemical (IHC) staining in 231 gastric cancer tumors. ANXA1 expression was positive in 108 cases (46.8%), whereas negative in 123 cases (53.2%). p53 expression was positive in 109 cases (47.2%), but negative in 122 cases (52.8%). The percentage of positive ANXA1 was significantly higher in p53 positive tumors compared with p53 negative tumors (P < 0.001). We next performed IHC staining for ANXA1 and p53 in three human gastric cancer cell lines (MKN28, NUGU4, KATOIII). Positive staining for ANXA1 and p53 was detected in MKN28 cells with TP53 gene mutations. On the other hand, weak positive staining for ANXA1 and positive staining for p53 was found in NUGC4 and KATOIII cells with TP53 wild-type and truncating mutations, respectively. Our results demonstrated that ANXA1 is upregulated in p53-positive gastric cancer. ANXA1 expression may be induced by aberrant p53 protein, providing the possibility that ANXA1 works with the TP53 gene in gastric cancer.

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Up-regulated Annexin A1 expression in gastrointestinal cancer is associated with cancer invasion and lymph node metastasis

Cited by 41 publications

References 23 publications

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

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

Identification of Annexin A1 protein expression in human gastric adenocarcinoma using proteomics and tissue microarray

Annexin A1 is upregulated in p53-positive gastric cancer

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