Annexin A2 in renal cell carcinoma: Expression, function, and prognostic significance1These authors contributed equally to this work

Shun Fa Yang, Han Lin Hsu, Tai Kuang Chao, Chia Jung Hsiao, Yung Feng Lin, Chao Wen Cheng

研究成果: 雜誌貢獻文章

16 引文 (Scopus)

摘要

Objective: Renal cell carcinoma (RCC) is the most lethal genitourinary cancer and intrinsically resistant to chemotherapy, radiotherapy, and hormone therapy. Annexin A2 (Anxa2) is a calcium-dependent phospholipid-binding protein found on various cell types that plays multiple roles in regulating cellular functions. In RCC, Anxa2 expression was correlated with tumor differentiation, clinical outcomes, and the metastatic potential; however, the underlying mechanisms remain obscure. This study investigated the role of Anxa2 in regulating tumorigenesis of RCC. Materials and methods: Commercial RCC tissue microarray arrays and a kidney cancer quantitative polymerase chain reaction array were used to examine Anxa2 by immunohistochemistry and real-time polymerase chain reaction analysis. Short hairpin (sh)RNA-based lentiviral system technology was used to evaluate the effects of manipulating Anxa2 expression on multiple malignant features of 2 RCC cell lines, A498 and 786-O, and its mechanisms. Results: (1) The Anxa2 expression level was generally elevated to varying degrees in RCC tissues. In adjacent noncancerous tissues, Anxa2 was mainly expressed in glomeruli and slightly expressed in the cytoplasm of proximal tubules. (2) An increased Anxa2 expression level was found in tissues of clear cell RCC, papillary RCC, and chromophobe RCC, and it was prominently expressed in cancer cell membranes. In addition, the Anxa2 expression level was correlated with poor prognosis. (3) Silencing Anxa2 expression suppressed the abilities of cell migration and invasion, but cell proliferation was less affected. (4) Diminished Anxa2 expression caused alterations in the cell polarity, disrupted the formation of actin filaments, and reduced CXCR4 expression. (5) Inhibition of the Rho/Rock axis restored silencing of Anxa2-mediated suppression of cell motility. Conclusions: Overall, our study points out the regulatory function of Anxa2 in RCC cell motility and provides a molecular-based mechanism of Anxa2 positivity in the progression of RCC.

原文英語
頁(從 - 到)22.e11-22.e21
期刊Urologic Oncology: Seminars and Original Investigations
33
發行號1
DOIs
出版狀態已發佈 - 一月 1 2015

指紋

Annexin A2
Annexins
Renal Cell Carcinoma
Cell Movement
Urogenital Neoplasms
Cell Polarity
Kidney Neoplasms
Actin Cytoskeleton

ASJC Scopus subject areas

  • Oncology
  • Urology

引用此文

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title = "Annexin A2 in renal cell carcinoma: Expression, function, and prognostic significance1These authors contributed equally to this work",
abstract = "Objective: Renal cell carcinoma (RCC) is the most lethal genitourinary cancer and intrinsically resistant to chemotherapy, radiotherapy, and hormone therapy. Annexin A2 (Anxa2) is a calcium-dependent phospholipid-binding protein found on various cell types that plays multiple roles in regulating cellular functions. In RCC, Anxa2 expression was correlated with tumor differentiation, clinical outcomes, and the metastatic potential; however, the underlying mechanisms remain obscure. This study investigated the role of Anxa2 in regulating tumorigenesis of RCC. Materials and methods: Commercial RCC tissue microarray arrays and a kidney cancer quantitative polymerase chain reaction array were used to examine Anxa2 by immunohistochemistry and real-time polymerase chain reaction analysis. Short hairpin (sh)RNA-based lentiviral system technology was used to evaluate the effects of manipulating Anxa2 expression on multiple malignant features of 2 RCC cell lines, A498 and 786-O, and its mechanisms. Results: (1) The Anxa2 expression level was generally elevated to varying degrees in RCC tissues. In adjacent noncancerous tissues, Anxa2 was mainly expressed in glomeruli and slightly expressed in the cytoplasm of proximal tubules. (2) An increased Anxa2 expression level was found in tissues of clear cell RCC, papillary RCC, and chromophobe RCC, and it was prominently expressed in cancer cell membranes. In addition, the Anxa2 expression level was correlated with poor prognosis. (3) Silencing Anxa2 expression suppressed the abilities of cell migration and invasion, but cell proliferation was less affected. (4) Diminished Anxa2 expression caused alterations in the cell polarity, disrupted the formation of actin filaments, and reduced CXCR4 expression. (5) Inhibition of the Rho/Rock axis restored silencing of Anxa2-mediated suppression of cell motility. Conclusions: Overall, our study points out the regulatory function of Anxa2 in RCC cell motility and provides a molecular-based mechanism of Anxa2 positivity in the progression of RCC.",
keywords = "Actin cytoskeleton, Annexin A2, Cell motility, Metastasis, Rho GTPase",
author = "Yang, {Shun Fa} and Hsu, {Han Lin} and Chao, {Tai Kuang} and Hsiao, {Chia Jung} and Lin, {Yung Feng} and Cheng, {Chao Wen}",
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TY - JOUR

T1 - Annexin A2 in renal cell carcinoma

T2 - Expression, function, and prognostic significance1These authors contributed equally to this work

AU - Yang, Shun Fa

AU - Hsu, Han Lin

AU - Chao, Tai Kuang

AU - Hsiao, Chia Jung

AU - Lin, Yung Feng

AU - Cheng, Chao Wen

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Objective: Renal cell carcinoma (RCC) is the most lethal genitourinary cancer and intrinsically resistant to chemotherapy, radiotherapy, and hormone therapy. Annexin A2 (Anxa2) is a calcium-dependent phospholipid-binding protein found on various cell types that plays multiple roles in regulating cellular functions. In RCC, Anxa2 expression was correlated with tumor differentiation, clinical outcomes, and the metastatic potential; however, the underlying mechanisms remain obscure. This study investigated the role of Anxa2 in regulating tumorigenesis of RCC. Materials and methods: Commercial RCC tissue microarray arrays and a kidney cancer quantitative polymerase chain reaction array were used to examine Anxa2 by immunohistochemistry and real-time polymerase chain reaction analysis. Short hairpin (sh)RNA-based lentiviral system technology was used to evaluate the effects of manipulating Anxa2 expression on multiple malignant features of 2 RCC cell lines, A498 and 786-O, and its mechanisms. Results: (1) The Anxa2 expression level was generally elevated to varying degrees in RCC tissues. In adjacent noncancerous tissues, Anxa2 was mainly expressed in glomeruli and slightly expressed in the cytoplasm of proximal tubules. (2) An increased Anxa2 expression level was found in tissues of clear cell RCC, papillary RCC, and chromophobe RCC, and it was prominently expressed in cancer cell membranes. In addition, the Anxa2 expression level was correlated with poor prognosis. (3) Silencing Anxa2 expression suppressed the abilities of cell migration and invasion, but cell proliferation was less affected. (4) Diminished Anxa2 expression caused alterations in the cell polarity, disrupted the formation of actin filaments, and reduced CXCR4 expression. (5) Inhibition of the Rho/Rock axis restored silencing of Anxa2-mediated suppression of cell motility. Conclusions: Overall, our study points out the regulatory function of Anxa2 in RCC cell motility and provides a molecular-based mechanism of Anxa2 positivity in the progression of RCC.

AB - Objective: Renal cell carcinoma (RCC) is the most lethal genitourinary cancer and intrinsically resistant to chemotherapy, radiotherapy, and hormone therapy. Annexin A2 (Anxa2) is a calcium-dependent phospholipid-binding protein found on various cell types that plays multiple roles in regulating cellular functions. In RCC, Anxa2 expression was correlated with tumor differentiation, clinical outcomes, and the metastatic potential; however, the underlying mechanisms remain obscure. This study investigated the role of Anxa2 in regulating tumorigenesis of RCC. Materials and methods: Commercial RCC tissue microarray arrays and a kidney cancer quantitative polymerase chain reaction array were used to examine Anxa2 by immunohistochemistry and real-time polymerase chain reaction analysis. Short hairpin (sh)RNA-based lentiviral system technology was used to evaluate the effects of manipulating Anxa2 expression on multiple malignant features of 2 RCC cell lines, A498 and 786-O, and its mechanisms. Results: (1) The Anxa2 expression level was generally elevated to varying degrees in RCC tissues. In adjacent noncancerous tissues, Anxa2 was mainly expressed in glomeruli and slightly expressed in the cytoplasm of proximal tubules. (2) An increased Anxa2 expression level was found in tissues of clear cell RCC, papillary RCC, and chromophobe RCC, and it was prominently expressed in cancer cell membranes. In addition, the Anxa2 expression level was correlated with poor prognosis. (3) Silencing Anxa2 expression suppressed the abilities of cell migration and invasion, but cell proliferation was less affected. (4) Diminished Anxa2 expression caused alterations in the cell polarity, disrupted the formation of actin filaments, and reduced CXCR4 expression. (5) Inhibition of the Rho/Rock axis restored silencing of Anxa2-mediated suppression of cell motility. Conclusions: Overall, our study points out the regulatory function of Anxa2 in RCC cell motility and provides a molecular-based mechanism of Anxa2 positivity in the progression of RCC.

KW - Actin cytoskeleton

KW - Annexin A2

KW - Cell motility

KW - Metastasis

KW - Rho GTPase

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