Axl as a downstream effector of TGF-β1 via PI3K/Akt-PAK1 signaling pathway promotes tumor invasion and chemoresistance in breast carcinoma

Tumor Biology

Volumn 36, Issue 2, 2015, Pages 1115-1127

  Li, Yanyan ^a   Jia, Li ^a   Liu, Chen ^a   Gong, Yanxin ^a   Ren, Dongliang ^a   Wang, Ning ^a   Zhang, Xu ^a   Zhao, Yongfu ^a  

^a DALIAN MEDICAL UNIVERSITY   (China)

Author keywords

Axl; Breast cancer; Chemosensitivity; Invasion; PI3K Akt PAK1; TGF 1

Indexed keywords

FLUOROURACIL; P21 ACTIVATED KINASE 1; PHOSPHATIDYLINOSITOL 3 KINASE; SHORT HAIRPIN RNA; TRANSFORMING GROWTH FACTOR BETA1; AXL RECEPTOR TYROSINE KINASE; ONCOPROTEIN; P21 ACTIVATED KINASE; PAK1 PROTEIN, HUMAN; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; AXL GENE; BREAST CARCINOMA; CANCER INHIBITION; CELL INVASION; CELL MOTILITY; CHEMOSENSITIVITY; CONTROLLED STUDY; DOWN REGULATION; DRUG SENSITIVITY; DRUG TISSUE LEVEL; ENZYME ACTIVATION; FEMALE; GENE; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; IC50; IMMUNOHISTOCHEMISTRY; IN VITRO STUDY; IN VIVO STUDY; LYMPH NODE METASTASIS; METASTASIS POTENTIAL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; RANDOMIZED CONTROLLED TRIAL; REAL TIME POLYMERASE CHAIN REACTION; RNA INTERFERENCE; RNA ISOLATION; SIGNAL TRANSDUCTION; TUMOR CELL; TUMOR DIFFERENTIATION; TUMOR INVASION; UPREGULATION; ANIMAL; BIOSYNTHESIS; BREAST TUMOR; DRUG RESISTANCE; GENETICS; MCF 7 CELL LINE; PATHOLOGY;

ANIMALS; BREAST NEOPLASMS; DRUG RESISTANCE, NEOPLASM; FEMALE; HUMANS; MCF-7 CELLS; MICE; NEOPLASM INVASIVENESS; P21-ACTIVATED KINASES; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTOR PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA;

EID: 84925533612     PISSN: 10104283     EISSN: 14230380     Source Type: Journal    
DOI: 10.1007/s13277-014-2677-3     Document Type: Article

References (35)

1. Yeh Y-Y, Chiao C-C, Kuo W-Y, Hsiao Y-C, Chen Y-J, Wei Y-Y, et al. TGF-β1 increases motility and αvβ3 integrin up-regulation via PI3K, Akt and NF-κB-dependent pathway in human chondrosarcoma cells. Biochem Pharmacol. 2008;75(6):1292–301.
2. Song X, Wang H, Logsdon CD, Rashid A, Fleming JB, Abbruzzese JL, et al. Overexpression of receptor tyrosine kinase Axl promotes tumor cell invasion and survival in pancreatic ductal adenocarcinoma. Cancer. 2011;117(4):734–43.
3. Linger R, Cohen R, Cummings C, Sather S, Migdall-Wilson J, Middleton D, et al. Mer or Axl receptor tyrosine kinase inhibition promotes apoptosis, blocks growth and enhances chemosensitivity of human non-small cell lung cancer. Oncogene. 2013;32(29):3420–31.
4. Benzakour O, Gely A, Lara R, Coronas V. Gas-6 and protein S: vitamin K-dependent factors and ligands for the TAM tyrosine kinase receptors family. Med Sci. 2007;23(10):826–33.
5. Shiozawa Y, Pedersen EA, Patel LR, Ziegler AM, Havens AM, Jung Y, et al. GAS6/AXL axis regulates prostate cancer invasion, proliferation, and survival in the bone marrow niche. Neoplasia (New York, NY). 2010;12(2):116.
6. Verma A, Warner SL, Vankayalapati H, Bearss DJ, Sharma S. Targeting Axl and Mer kinases in cancer. Mol Cancer Ther. 2011;10(10):1763–73.
7. Korshunov VA. Axl-dependent signalling: a clinical update. Clin Sci. 2012;122(8):361–8.
8. Sasaki T, Knyazev PG, Clout NJ, Cheburkin Y, Göhring W, Ullrich A, et al. Structural basis for Gas6–Axl signalling. EMBO J. 2006;25(1):80–7.
9. Lee H-J, Jeng Y-M, Chen Y-L, Chung L, Yuan R-H. Gas6/Axl pathway promotes tumor invasion through the transcriptional activation of Slug in hepatocellular carcinoma. Carcinogenesis. 2013:bgt372.
10. Alvarez H, Montgomery EA, Karikari C, Canto M, Dunbar KB, Wang JS, et al. The Axl receptor tyrosine kinase is an adverse prognostic factor and a therapeutic target in esophageal adenocarcinoma. Cancer Biol Ther. 2010;10(10):1009.
11. Avilla E, Guarino V, Visciano C, Liotti F, Svelto M, Krishnamoorthy G, et al. Activation of TYRO3/AXL tyrosine kinase receptors in thyroid cancer. Cancer Res. 2011;71(5):1792–804.
12. Wu C-W, Li A, Chi C-W, Lai C-H, Huang CL, Lo S-S, et al. Clinical significance of AXL kinase family in gastric cancer. Anticancer Res. 2001;22(2B):1071–8.
13. Shieh Y-S, Lai C-Y, Kao Y-R, Shiah S-G, Chu Y-W, Lee H-S, et al. Expression of axl in lung adenocarcinoma and correlation with tumor progression. Neoplasia (New York, NY). 2005;7(12):1058.
14. Xu M, Chan S, Liu A, Wong K, Fan S, Chen J, et al. AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma. Oncogene. 2011;30(10):1229–40.
15. Holland SJ, Powell MJ, Franci C, Chan EW, Friera AM, Atchison RE, et al. Multiple roles for the receptor tyrosine kinase axl in tumor formation. Cancer Res. 2005;65:9294–303.
16. Linger R, Keating AK, Earp HS, Graham DK. Tam receptor tyrosine kinases: biologic functions, signaling, and potential therapeutic targeting in human cancer. Adv Cancer Res. 2008;100:35–83.
17. Son B-K, Kozaki K, Iijima K, Eto M, Nakano T, Akishita M, et al. Gas6/axl-pi3k/akt pathway plays a central role in the effect of statins on inorganic phosphate-induced calcification of vascular smooth muscle cells. Eur J Pharmacol. 2007;556:1–8.
18. Araki S, Eitel JA, Batuello CN, Bijangi-Vishehsaraei K, Xie X-J, Danielpour D, et al. TGF-β1–induced expression of human Mdm2 correlates with late-stage metastatic breast cancer. J Clin Invest. 2010;120(1):290.
19. Wu J, Ru N, Zhang Y, Li Y, Wei D, Ren Z, et al. HAb18G/CD147 promotes epithelial–mesenchymal transition through TGF-β signaling and is transcriptionally regulated by Slug. Oncogene. 2011;30(43):4410.
20. Tsushima H, Ito N, Tamura S, Matsuda Y, Inada M, Yabuuchi I, et al. Circulating transforming growth factor β1 as a predictor of liver metastasis after resection in colorectal cancer. Clin Cancer Res. 2001;7(5):1258–62.
21. Shim KS, Kim KH, Han WS, Park EB. Elevated serum levels of transforming growth factor-β1 in patients with colorectal carcinoma. Cancer. 1999;85(3):554–61.
22. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7(8):606–19.
23. Bellacosa A, Kumar CC, Cristofano AD, Testa JR. Activation of AKT kinases in cancer: implications for therapeutic targeting. Adv Cancer Res. 2005;94:29–86.
24. Melaragno MG, Cavet ME, Yan C, Tai L-K, Jin Z-G, Haendeler J, et al. Gas6 inhibits apoptosis in vascular smooth muscle: role of Axl kinase and Akt. J Mol Cell Cardiol. 2004;37(4):881–7.
25. Osaki M. Oshimura Ma, Ito H. PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis. 2004;9(6):667–76.
26. Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004;4(5):361–70.
27. Xu J, Jia L, Ma H, Li Y, Ma Z, Zhao Y. Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma via PI3K/Akt-PAK1 signal pathway. Tumor Biol. 2013:1–9.
28. Zhao Y, Sun X, Jiang L, Yang F, Zhang Z, Jia L. Differential expression of Axl and correlation with invasion and multidrug resistance in cancer cells. Cancer Investig. 2012;30(4):287–94.
29. Bauer T, Zagórska A, Jurkin J, Yasmin N, Köffel R, Richter S, et al. Identification of Axl as a downstream effector of TGF-β1 during Langerhans cell differentiation and epidermal homeostasis. J Exp Med. 2012;209(11):2033–47.
30. Berclaz G, Altermatt H, Rohrbach V, Kieffer I, Dreher E, Andres A-C. Estrogen dependent expression of the receptor tyrosine kinase axl in normal and malignant human breast. Ann Oncol. 2001;12(6):819–24.
31. Li J, Jia L, Ma Z-H, Ma Q-H, Yang X-H, Zhao Y-F. Axl glycosylation mediates tumor cell proliferation, invasion and lymphatic metastasis in murine hepatocellular carcinoma. World J Gastroenterol: WJG. 2012;18(38):5369.
32. Wiercinska E, Naber HP, Pardali E, van der Pluijm G, van Dam H, ten Dijke P. The tgf-β/smad pathway induces breast cancer cell invasion through the up-regulation of matrix metalloproteinase 2 and 9 in a spheroid invasion model system. Breast Cancer Res Treat. 2011;128:657–66.
33. Li J, Weinberg MS, Zerbini L, Prince S. The oncogenic tbx3 is a downstream target and mediator of the tgf-β1 signaling pathway. Mol Biol Cell. 2013;24:3569–76.
34. Kim YS, Jung DH, Sohn E, Kim J, Kim JS. Glycoxidised LDL induced the upregulation of Axl receptor tyrosine kinase and its ligand in mouse mesangial cells. PLoS One. 2012;7(11):e50297.
35. Clauser S, Meilhac O, Bieche I, Raynal P, Bruneval P, Michel J-B, et al. Increased secretion of Gas6 by smooth muscle cells in human atherosclerotic carotid plaques. Thromb Haemost. 2012;107(1):140.