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Erschienen in: Tumor Biology 2/2014

01.02.2014 | Research Article

ASAP3 expression in non-small cell lung cancer: association with cancer development and patients’ clinical outcome

verfasst von: Chuifeng Fan, Yuan Tian, Yuan Miao, Xuyong Lin, Xiupeng Zhang, Guiyang Jiang, Lan Luan, Enhua Wang

Erschienen in: Tumor Biology | Ausgabe 2/2014

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Abstract

ASAP3 belongs to Arf-specific GTPase-activating proteins which regulate Arfs by stimulating their intrinsic GTP hydrolysis. ASAP3 expression and the clinical significance in malignant tumors are largely unknown. In this study, we examined ASAP3 expression in non-small cell lung cancer (NSCLC) to find out its clinicopathological significance. Immunohistochemistry shows elevated expression of ASAP3 in cancer tissues (54.8 % (57/104)) compared to normal lung tissues (18.0 % (9/50)) (p < 0.05). Increased ASAP3 expression was associated with poor differentiation, lymph node metastasis, and advanced TNM stages in NSCLC (p < 0.05). Survival analysis reveals that ASAP3 expression contributes to patients’ poor clinical outcome (p < 0.05). We also examined ASAP3 expression in several lung cancer cell lines using Western blotting. We downregulated ASAP3 expression in LTE cell which has a relative high level of ASAP3 expression using siRNA and found that reduced ASAP3 leads to significant inhibition of cancer cell invasion (p < 0.05). These data indicate that ASAP3 is elevated in NSCLC and may contribute to cancer development and patients’ poor clinical outcome, which is possibly due to its critical roles in regulating cancer invasion.
Literatur
1.
Zurück zum Zitat Donaldson JG. Multiple roles for Arf6: sorting, structuring, and signaling at the plasma membrane. J Biol Chem. 2003;278(43):41573–6.PubMedCrossRef Donaldson JG. Multiple roles for Arf6: sorting, structuring, and signaling at the plasma membrane. J Biol Chem. 2003;278(43):41573–6.PubMedCrossRef
2.
Zurück zum Zitat Donaldson JG, Honda A, Weigert R. Multiple activities for Arf1 at the Golgi complex. Biochim Biophys Acta. 2005;1744(3):364–73.PubMedCrossRef Donaldson JG, Honda A, Weigert R. Multiple activities for Arf1 at the Golgi complex. Biochim Biophys Acta. 2005;1744(3):364–73.PubMedCrossRef
3.
Zurück zum Zitat Kahn RA, Cherfils J, Elias M, Lovering RC, Munro S, Schurmann A. Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins. J Cell Biol. 2006;172:645–50.PubMedCrossRef Kahn RA, Cherfils J, Elias M, Lovering RC, Munro S, Schurmann A. Nomenclature for the human Arf family of GTP-binding proteins: ARF, ARL, and SAR proteins. J Cell Biol. 2006;172:645–50.PubMedCrossRef
4.
Zurück zum Zitat Turner CE, West KA, Brown MC. Paxillin-ARF GAP signaling and the cytoskeleton. Curr Opin Cell Biol. 2001;13(5):593–9.PubMedCrossRef Turner CE, West KA, Brown MC. Paxillin-ARF GAP signaling and the cytoskeleton. Curr Opin Cell Biol. 2001;13(5):593–9.PubMedCrossRef
5.
Zurück zum Zitat Sabe H, Onodera Y, Mazaki Y, Hashimoto S. ArfGAP family proteins in cell adhesion, migration and tumor invasion. Curr Opin Cell Biol. 2006;18(5):558–64.PubMedCrossRef Sabe H, Onodera Y, Mazaki Y, Hashimoto S. ArfGAP family proteins in cell adhesion, migration and tumor invasion. Curr Opin Cell Biol. 2006;18(5):558–64.PubMedCrossRef
6.
Zurück zum Zitat Kahn RA, Bruford E, Inoue H, Logsdon Jr JM, Nie Z, Premont RT, et al. Consensus nomenclature for the human ArfGAP domain-containing proteins. J Cell Biol. 2008;182(6):1039–44.PubMedCrossRef Kahn RA, Bruford E, Inoue H, Logsdon Jr JM, Nie Z, Premont RT, et al. Consensus nomenclature for the human ArfGAP domain-containing proteins. J Cell Biol. 2008;182(6):1039–44.PubMedCrossRef
7.
Zurück zum Zitat Hiroshi O, Yoichi F, Tatsushi K, Suguru H. Isolation of development and differentiation enhancing factor-like 1 (DDEFL1) as a drug target for hepatocellular carcinomas. Int J Oncol. 2004;24:43–8. Hiroshi O, Yoichi F, Tatsushi K, Suguru H. Isolation of development and differentiation enhancing factor-like 1 (DDEFL1) as a drug target for hepatocellular carcinomas. Int J Oncol. 2004;24:43–8.
8.
Zurück zum Zitat Vi LH, Sanita B, Hiroki I, William CV, Fanny C, Zhong ZN, et al. ASAP3 is a focal adhesion-associated Arf GAP that functions in cell migration and invasion. J Biol Chem. 2008;283(22):14915–26.CrossRef Vi LH, Sanita B, Hiroki I, William CV, Fanny C, Zhong ZN, et al. ASAP3 is a focal adhesion-associated Arf GAP that functions in cell migration and invasion. J Biol Chem. 2008;283(22):14915–26.CrossRef
9.
Zurück zum Zitat Shehab AI, Ingrid RV, Begona S, Alfred W. The structure of an Arf-ArfGAP complex reveals a Ca2+ regulatory mechanism. Cell. 2010;141:812–21.CrossRef Shehab AI, Ingrid RV, Begona S, Alfred W. The structure of an Arf-ArfGAP complex reveals a Ca2+ regulatory mechanism. Cell. 2010;141:812–21.CrossRef
10.
Zurück zum Zitat Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (7th) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2:706–14.PubMedCrossRef Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The IASLC lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (7th) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2:706–14.PubMedCrossRef
11.
Zurück zum Zitat Travis WDBE, Muller-Hermelink HK, Harris CC. World health organization classification of tumors: pathology and genetics of tumors of the lung, pleura, thymus and heart. Lyon: IARC; 2004. Travis WDBE, Muller-Hermelink HK, Harris CC. World health organization classification of tumors: pathology and genetics of tumors of the lung, pleura, thymus and heart. Lyon: IARC; 2004.
12.
Zurück zum Zitat Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6:244–85.PubMedCrossRef Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, et al. International association for the study of lung cancer/American thoracic society/European respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol. 2011;6:244–85.PubMedCrossRef
13.
Zurück zum Zitat Randazzo PA, Andrade J, Miura K, Brown MT, Long YQ, Stauffer S, et al. The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton. Proc Natl Acad Sci U S A. 2000;97(8):4011–6.PubMedCentralPubMedCrossRef Randazzo PA, Andrade J, Miura K, Brown MT, Long YQ, Stauffer S, et al. The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton. Proc Natl Acad Sci U S A. 2000;97(8):4011–6.PubMedCentralPubMedCrossRef
14.
Zurück zum Zitat Furman C, Short SM, Subramanian RR, Zetter BR, Roberts TM. DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism. J Biol Chem. 2002;277(10):7962–9.PubMedCrossRef Furman C, Short SM, Subramanian RR, Zetter BR, Roberts TM. DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism. J Biol Chem. 2002;277(10):7962–9.PubMedCrossRef
15.
Zurück zum Zitat Liu Y, Loijens JC, Martin KH, Karginov AV, Parsons JT. The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly. Mol Biol Cell. 2002;13(6):2147–56.PubMedCentralPubMedCrossRef Liu Y, Loijens JC, Martin KH, Karginov AV, Parsons JT. The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly. Mol Biol Cell. 2002;13(6):2147–56.PubMedCentralPubMedCrossRef
Metadaten
Titel
ASAP3 expression in non-small cell lung cancer: association with cancer development and patients’ clinical outcome
verfasst von
Chuifeng Fan
Yuan Tian
Yuan Miao
Xuyong Lin
Xiupeng Zhang
Guiyang Jiang
Lan Luan
Enhua Wang
Publikationsdatum
01.02.2014
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 2/2014
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1205-1

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