#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Rab Proteins, Intracellular Transport and Cancer


Authors: R. Černochová;  M. Nekulová;  J. Holčáková
Authors place of work: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in the journal: Klin Onkol 2016; 29(Supplementum 4): 31-39
Category: Review
doi: https://doi.org/10.14735/amko20164S31

Summary

Background:
Rab proteins are small monomeric enzymes which belong to the large Ras protein superfamily and allow hydrolysis of guanosine triphosphate (GTP) to guanosine (GDP). Up to now more than 60 proteins have been described that act primarily as regulators of intracellular transport. Rab GTPases are mostly located at the intracellular membranes, where they provide connections to motor proteins and to the cytoskeleton and control various steps of the traffic pathways including the formation and movement of vesicles or membrane fusion controlling secretion, endocytosis, recycling and degradation of proteins. Today, the deregulated expression of Rab protein is discussed in different types of malignancies. The number of identified diseases associated with mutations in Rab proteins or their cooperating partners increases and the evidence for the involvement of Rab to the human pathologies such as the immune failure, obesity and diabetes, Alzheimer‘s disease or hereditary genetic diseases is growing. The malfunctions of Rab proteins caused by mutations or aberrant posttranslational modifications lead to changes in the protein and vesicle trafficking, which play a crucial role in the formation and development of cancer and the deregulation of Rab expression frequently influences the migration, invasion, proliferation and drug resistance of the tumor cells.

Aims:
This article summarizes the main functions of Rab proteins in the cells, describes the mechanism of their activity and focuses on the current knowledge about the roles of these GTPases in carcinogenesis.

Key words:
Rab GTPases – protein transport – carcinogenesis

This work was supported by the project MEYS – NPS I – LO1413.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Submitted:
13. 5. 2016

Accepted:
31. 5. 2016


Zdroje

1. Hutagalung AH, Novick PJ. Role of Rab GTPases in membrane traffic and cell physiology. Physiol Rev 2011; 91 (1): 119–149. doi: 10.1152/physrev.00059.2009.

2. Mitra S, Cheng KW, Mills GB. Rab GTPases implicated in inherited and acquired disorders. Semin Cell Dev Biol 2011; 22 (1): 57–68. doi: 10.1016/j.semcdb.2010.12.005.

3. Brighouse A, Dacks JB, Field MC. Rab protein evolution and the history of the eukaryotic endomembrane system. Cell Mol Life Sci 2010; 67 (20): 3449–3465. doi: 10.1007/s00018-010-0436-1.

4. Scita G, Di Fiore PP. The endocytic matrix. Nature 2010; 463 (7280): 464–473. doi: 10.1038/nature08910.

5. Cottam NP, Ungar D. Retrograde vesicle transport in the Golgi. Protoplasma 2012; 249 (4): 943–955.

6. Beck R, Rawet M, Wieland FT et al. The COPI system: molecular mechanisms and function. FEBS Lett 2009; 583 (17): 2701–2709. doi: 10.1016/j.febslet.2009.07.032.

7. Nakano A, Luini A. Passage through the Golgi. Curr Opin Cell Biol 2010; 22 (4): 471–478. doi: 10.1016/j.ceb.2010.05.003.

8. Ng EL, Gan BQ, Ng F et al. Rab GTPases regulating receptor trafficking at the late endosome-lysosome membranes. Cell Biochem Funct 2012; 30 (6): 515–523. doi: 10.1002/cbf.2827.

9. Zhang J, Fonovic M, Suyama K et al. Rab35 controls actin bundling by recruiting fascin as an effector protein. Science 2009; 325 (5945): 1250–1254. doi: 10.1126/science.1174921.

10. Seabra MC, Mules EH, Hume AN. Rab GTPases, intracellular traffic and disease. Trends Mol Med 2002; 8 (1): 23–30.

11. Pereira-Leal JB, Seabra MC. The mammalian Rab family of small GTPases: definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily. J Mol Biol 2000; 301 (4): 1077–1087.

12. Bhuin T, Roy JK. Rab proteins: the key regulators of intracellular vesicle transport. Exp Cell Res 2014; 328 (1): 1–19. doi: 10.1016/j.yexcr.2014.07.027.

13. Li F, Yi L, Zhao L et al. The role of the hypervariable C-terminal domain in Rab GTPases membrane targeting. Proc Natl Acad Sci U S A 2014; 111 (7): 2572–2577. doi: 10.1073/pnas.1313655111.

14. Gomes AQ, Ali BR, Ramalho JS et al. Membrane targeting of Rab GTPases is influenced by the prenylation motif. Mol Biol Cell 2003; 14 (5): 1882–1899.

15. Wu YW, Tan KT, Waldmann H et al. Interaction analysis of prenylated Rab GTPase with Rab escort protein and GDP dissociation inhibitor explains the need for both regulators. Proc Natl Acad Sci U S A 2007; 104 (30): 12294–12299.

16. Barr F, Lambright DG. Rab GEFs and GAPs. Curr Opin Cell Biol 2010; 22 (4): 461–470. doi: 10.1016/j.ceb.2010.04.007.

17. Dumas JJ, Zhu Z, Connolly JL et al. Structural basis of activation and GTP hydrolysis in Rab proteins. Structure 1999; 7 (4): 413–423.

18. Pan X, Eathiraj S, Munson M et al. TBC-domain GAPs for Rab GTPases accelerate GTP hydrolysis by a dual-finger mechanism. Nature 2006; 442 (7100): 303–306.

19. Stenmark H. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 2009; 10 (8): 513–525. doi: 10.1038/nrm2728.

20. Epp N, Rethmeier R, Kramer L et al. Membrane dynamics and fusion at late endosomes and vacuoles-Rab regulation, multisubunit tethering complexes and SNAREs. Eur J Cell Biol 2011; 90 (9): 779–785. doi: 10.1016/j.ejcb.2011.04.007.

21. Dirac-Svejstrup AB, Sumizawa T, Pfeffer SR. Identification of a GDI displacement factor that releases endosomal Rab GTPases from Rab-GDI. EMBO J 1997; 16 (3): 465–472.

22. Kawasaki M, Nakayama K, Wakatsuki S. Membrane recruitment of effector proteins by Arf and Rab GTPases. Curr Opin Struct Biol 2005; 15 (6): 681–689.

23. Sztul E, Lupashin V. Role of tethering factors in secretory membrane traffic. Am J Physiol Cell Physiol 2006; 290 (1): C11–C26.

24. Chia PZ, Gleeson PA. Membrane tethering. F1000Prime Rep 2014; 6: 74. doi: 10.12703/P6-74.

25. Brocker C, Engelbrecht-Vandre S, Ungermann C. Multisubunit tethering complexes and their role in membrane fusion. Curr Biol 2010; 20 (21): R943–R952. doi: 10.1016/j.cub.2010.09.015.

26. Yu IM, Hughson FM. Tethering factors as organizers of intracellular vesicular traffic. Annu Rev Cell Dev Biol 2010; 26: 137–156. doi: 10.1146/annurev.cellbio.042308.113327.

27. Jahn R, Lang T, Sudhof TC. Membrane fusion. Cell 2003; 112 (4): 519–533.

28. Ortiz Sandoval C, Simmen T. Rab proteins of the endoplasmic reticulum: functions and interactors. Biochem Soc Trans 2012; 40 (6): 1426–1432. doi: 10.1042/BST20120158.

29. Gillingham AK, Sinka R, Torres IL et al. Toward a comprehensive map of the effectors of rab GTPases. Dev Cell 2014; 31 (3): 358–373. doi: 10.1016/j.devcel.2014.10.007.

30. Recchi C, Seabra MC. Novel functions for Rab GTPases in multiple aspects of tumour progression. Biochem Soc Trans 2012; 40 (6): 1398–1403. doi: 10.1042/BST20120199.

31. Shimada K, Uzawa K, Kato M et al. Aberrant expression of RAB1A in human tongue cancer. Br J Cancer 2005; 92 (10): 1915–1921.

32. Thomas JD, Zhang YJ, Wei YH et al. Rab1A is an mTORC1 activator and a colorectal oncogene. Cancer Cell 2014; 26 (5): 754–769. doi: 10.1016/j.ccell.2014.09.008.

33. Sun T, Wang X, He HH et al. MiR-221 promotes the development of androgen independence in prostate cancer cells via downregulation of HECTD2 and RAB1A. Oncogene 2014; 33 (21): 2790–2800. doi: 10.1038/onc.2013.230.

34. Jiang HL, Sun HF, Gao SP et al. Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-beta/SMAD signaling. Oncotarget 2015; 6 (18): 16352–16365.

35. Zhai H, Song B, Xu X et al. Inhibition of autophagy and tumor growth in colon cancer by miR-502. Oncogene 2013; 32 (12): 1570–1579. doi: 10.1038/onc.2012.167.

36. Kim JK, Lee SY, Park CW et al. Rab3a promotes brain tumor initiation and progression. Mol Biol Rep 2014; 41 (9): 5903–5911. doi: 10.1007/s11033-014-3465-2.

37. Liu Q, Tang H, Liu X et al. miR-200b as a prognostic factor targets multiple members of RAB family in glioma. Med Oncol 2014; 31 (3): 859. doi: 10.1007/s12032-014-0859-x.

38. Ye F, Tang H, Liu Q et al. miR-200b as a prognostic factor in breast cancer targets multiple members of RAB family. J Transl Med 2014; 12: 17. doi: 10.1186/1479-5876-12-17.

39. Pan Y, Wang R, Zhang F et al. MicroRNA-130a inhibits cell proliferation, invasion and migration in human breast cancer by targeting the RAB5A. Int J Clin Exp Pathol 2015; 8 (1): 384–393.

40. Yang PS, Yin PH, Tseng LM et al. Rab5A is associated with axillary lymph node metastasis in breast cancer patients. Cancer Sci 2011; 102 (12): 2172–2178. doi: 10.1111/j.1349-7006.2011.02089.x.

41. Chen Q, Liu WY, Zhao Z et al. Expression and significance of Rab5a and APPL1 in breast cancer. Zhonghua Zhong Liu Za Zhi 2012; 34 (11): 838–841. doi: 10.3760/ cma.j.issn.0253-3766.2012.11.009.

42. Huang H, Jiang Y, Wang Y et al. miR-5100 promotes tumor growth in lung cancer by targeting Rab6. Cancer Lett 2015; 362 (1): 15–24. doi: 10.1016/j.canlet.2015.03.004.

43. Alonso-Curbelo D, Osterloh L, Canon E et al. RAB7 counteracts PI3K-driven macropinocytosis activated at early stages of melanoma development. Oncotarget 2015; 6 (14): 11848–11862.

44. Nakano T, Shimizu K, Kawashima O et al. Establishment of a human lung cancer cell line with high metastatic potential to multiple organs: gene expression associated with metastatic potential in human lung cancer. Oncol Rep 2012; 28 (5): 1727–1735. doi: 10.3892/or.2012.1 972.

45. Lin Z, Li JW, Wang Y et al. Abnormal miRNA-30e expression is associated with breast cancer progression. Clin Lab 2016; 62 (1–2): 121–128.

46. Qi J, Zhao P, Li F et al. Down-regulation of Rab17 promotes tumourigenic properties of hepatocellular carcinoma cells via Erk pathway. Int J Clin Exp Pathol 2015; 8 (5): 4963–4971.

47. Wang K, Mao Z, Liu L et al. Rab17 inhibits the tumourigenic properties of hepatocellular carcinomas via the Erk pathway. Tumour Biol 2015; 36 (8): 5815–5824. doi: 10.1007/s13277-015-3251-3.

48. Zhong K, Chen K, Han L et al. MicroRNA-30b/c inhibits non-small cell lung cancer cell proliferation by targeting Rab18. BMC Cancer 2014; 14: 703. doi: 10.1186/1471-2407-14-703.

49. Hou Q, Wu YH, Grabsch H et al. Integrative genomics identifies RAB23 as an invasion mediator gene in diffuse-type gastric cancer. Cancer Res 2008; 68 (12): 4623–4630. doi: 10.1158/0008-5472.CAN-07-5870.

50. Jiang Y, Han Y, Sun C et al. Rab23 is overexpressed in human bladder cancer and promotes cancer cell proliferation and invasion. Tumour Biol 2015; 37 (6): 8131–8138. doi: 10.1007/s13277-015-4590-9.

51. Liu YJ, Wang Q, Li W et al. Rab23 is a potential biological target for treating hepatocellular carcinoma. World J Gastroenterol 2007; 13 (7): 1010–1017.

52. Geng D, Zhao W, Feng Y et al. Overexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion. Tumour Biol 2015; 37 (6): 7713–7718. doi: 10.1007/s13277-015-4606-5.

53. Amornphimoltham P, Rechache K, Thompson J et al. Rab25 regulates invasion and metastasis in head and neck cancer. Clin Cancer Res 2013; 19 (6): 1375–1388. doi: 10.1158/1078-0432.CCR-12-2858.

54. Ma YF, Yang B, Li J et al. Expression of Ras-related protein 25 predicts chemotherapy resistance and prognosis in advanced non-small cell lung cancer. Genet Mol Res 2015; 14 (4): 13998–14008.

55. Li Y, Jia Q, Zhang Q et al. Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma. Biochem Biophys Res Commun 2015; 458 (4): 745–750. doi: 10.4238/2015.

56. Liu L, Ding G. Rab25 expression predicts poor prognosis in clear cell renal cell carcinoma. Exp Ther Med 2014; 8 (4): 1055–1058.

57. No JH, Kim K, Park KH et al. Cell-free DNA level as a prognostic biomarker for epithelial ovarian cancer. Anticancer Res 2012; 32 (8): 3467–3471.

58. Yin YX, Shen F, Pei H et al. Increased expression of Rab25 in breast cancer correlates with lymphatic metastasis. Tumour Biol 2012; 33 (5): 1581–1587. doi: 10.1007/s13277-012-0412-5.

59. Gomez-Roman N, Sahasrabudhe NM, McGregor F et al. Hypoxia-inducible factor 1 alpha is required for the tumourigenic and aggressive phenotype associated with Rab25 expression in ovarian cancer. Oncotarget 2016; 7 (16): 22650–22664. doi: 10.18632/oncotarget.7998.

60. Zhao H, Wang Q, Wang X et al. Correlation between RAB27B and p53 expression and overall survival in pancreatic cancer. Pancreas 2016; 45 (2): 204–210. doi: 10.1097/MPA.0000000000000453.

61. Sui Y, Zheng X, Zhao D. Rab31 promoted hepatocellular carcinoma (HCC) progression via inhibition of cell apoptosis induced by PI3K/AKT/Bcl-2/BAX pathway. Tumour Biol 2015; 36 (11): 8661–8670. doi: 10.1007/s13277-015-3626-5.

62. Kotzsch M, Sieuwerts AM, Grosser M et al. Urokinase receptor splice variant uPAR-del4/5-associated gene expression in breast cancer: identification of rab31 as an independent prognostic factor. Breast Cancer Res Treat 2008; 111 (2): 229–240.

63. Shibata D, Mori Y, Cai K et al. RAB32 hypermethylation and microsatellite instability in gastric and endometrial adenocarcinomas. Int J Cancer 2006; 119 (4): 801–806.

64. Mori Y, Yin J, Sato F et al. Identification of genes uniquely involved in frequent microsatellite instability colon carcinogenesis by expression profiling combined with epigenetic scanning. Cancer Res 2004; 64 (7): 2434–2438.

65. Wang HJ, Gao Y, Chen L et al. RAB34 was a progression- and prognosis-associated biomarker in gliomas. Tumour Biol 2015; 36 (3): 1573–1578. doi: 10.1007/s13277-014-2732-0.

66. Wu CY, Tseng RC, Hsu HS et al. Frequent down-regulation of hRAB37 in metastatic tumor by genetic and epigenetic mechanisms in lung cancer. Lung Cancer 2009; 63 (3): 360–367. doi: 10.1016/j.lungcan.2008.06.014.

67. Wang H, Jiang C. RAB38 confers a poor prognosis, associated with malignant progression and subtype preference in glioma. Oncol Rep 2013; 30 (5): 2350–2356. doi: 10.3892/or.2013.2730.

68. Li Y, Jia Q, Wang Y et al. Rab40b upregulation correlates with the prognosis of gastric cancer by promoting migration, invasion, and metastasis. Med Oncol 2015; 32 (4): 126. doi: 10.1007/s12032-015-0562-6.

69. Rhodes DR, Kalyana-Sundaram S, Mahavisno V et al. Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia 2007; 9 (2): 166–180.

70. He H, Dai F, Yu L et al. Identification and characterization of nine novel human small GTPases showing variable expressions in liver cancer tissues. Gene Expr 2002; 10 (5–6): 231–242.

71. Amillet JM, Ferbus D, Real FX et al. Characterization of human Rab20 overexpressed in exocrine pancreatic carcinoma. Hum Pathol 2006; 37 (3): 256–263.

72. Turner N, Lambros MB, Horlings HM et al. Integrative molecular profiling of triple negative breast cancers identifies amplicon drivers and potential therapeutic targets. Oncogene 2010; 29 (14): 2013–2023. doi: 10.1038/onc.2009.489.

73. Luo H, Zhang H, Zhang Z et al. Down-regulated miR-9 and miR-433 in human gastric carcinoma. J Exp Clin Cancer Res 2009; 28: 82. doi: 10.1186/1756-9966-28-82.

74. Yang Q, Jie Z, Cao H et al. Low-level expression of let-7a in gastric cancer and its involvement in tumorigenesis by targeting RAB40C. Carcinogenesis 2011; 32 (5): 713–722. doi: 10.1093/carcin/bgr035.

75. Tanaka T, Arai M, Wu S et al. Epigenetic silencing of microRNA-373 plays an important role in regulating cell proliferation in colon cancer. Oncol Rep 2011; 26 (5): 1329–1335. doi: 10.3892/or.2011.1401.

76. Li G. Rab GTPases, membrane trafficking and diseases. Curr Drug Targets 2011; 12 (8): 1188–1193.

77. Rodriguez-Gabin AG, Cammer M, Almazan G et al. Role of rRAB22b, an oligodendrocyte protein, in regulation of transport of vesicles from trans Golgi to endocytic compartments. J Neurosci Res 2001; 66 (6): 1149–1160.

78. Cheng KW, Lahad JP, Gray JW et al. Emerging role of RAB GTPases in cancer and human disease. Cancer Res 2005; 65 (7): 2516–2519.

79. Cheng KW, Lahad JP, Kuo WL et al. The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med 2004; 10 (11): 1251–1256.

80. Fan Y, Xin XY, Chen BL et al. Knockdown of RAB25 expression by RNAi inhibits growth of human epithelial ovarian cancer cells in vitro and in vivo. Pathology 2006; 38 (6): 561–567.

81. Caswell PT, Spence HJ, Parsons M et al. Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments. Dev Cell 2007; 13 (4): 496–510.

82. Fan Y, Wang L, Han X et al. Rab25 is responsible for phosphoinositide 3-kinase/AKTmediated cisplatin resistance in human epithelial ovarian cancer cells. Mol Med Rep 2015; 11 (3): 2173–2178. doi: 10.3892/mmr.2014.2963.

83. Korkola JE, Heck S, Olshen AB et al. In vivo differentiation and genomic evolution in adult male germ cell tumors. Genes Chromosomes Cancer 2008; 47 (1): 43–55.

84. Agarwal R, Jurisica I, Mills GB et al. The emerging role of the RAB25 small GTPase in cancer. Traffic 2009; 10 (11): 1561–1568. doi: 10.1111/j.1600-0854.2009.00969.x.

85. Mor O, Nativ O, Stein A et al. Molecular analysis of transitional cell carcinoma using cDNA microarray. Oncogene 2003; 22 (48): 7702–7710.

86. Cheng JM, Ding M, Aribi A et al. Loss of RAB25 expression in breast cancer. Int J Cancer 2006; 118 (12): 2957–2964.

87. Nam KT, Lee HJ, Smith JJ et al. Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas. J Clin Invest 2010; 120 (3): 840–849. doi: 10.1172/JCI40728.

88. Hales CM, Griner R, Hobdy-Henderson KC et al. Identification and characterization of a family of Rab11-interacting proteins. J Biol Chem 2001; 276 (42): 39067–39075.

89. Caswell PT, Chan M, Lindsay AJ et al. Rab-coupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments. J Cell Biol 2008; 183 (1): 143–155. doi: 10.1083/jcb.200804140.

90. Yoon SO, Shin S, Mercurio AM. Hypoxia stimulates carcinoma invasion by stabilizing microtubules and promoting the Rab11 trafficking of the alpha6beta4 integrin. Cancer Res 2005; 65 (7): 2761–2769.

91. Pellinen T, Arjonen A, Vuoriluoto K et al. Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins. J Cell Biol 2006; 173 (5): 767–780.

92. Mendoza P, Diaz J, Silva P et al. Rab5 activation as a tumor cell migration switch. Small GTPases 2014; 5 (1).

93. Hooper S, Gaggioli C, Sahai E. A chemical biology screen reveals a role for Rab21-mediated control of actomyosin contractility in fibroblast-driven cancer invasion. Br J Cancer 2010; 102 (2): 392–402. doi: 10.1038/sj.bjc.6605469.

94. Rink J, Ghigo E, Kalaidzidis Y et al. Rab conversion as a mechanism of progression from early to late endosomes. Cell 2005; 122 (5): 735–749.

95. Li Y, Meng X, Feng H et al. Over-expression of the RAB5 gene in human lung adenocarcinoma cells with high metastatic potential. Chin Med Sci J 1999; 14 (2): 96–101.

96. Fukui K, Tamura S, Wada A et al. Expression of Rab5a in hepatocellular carcinoma: possible involvement in epidermal growth factor signaling. Hepatol Res 2007; 37 (11): 957–965.

97. Bravo-Cordero JJ, Marrero-Diaz R, Megias D et al. MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. EMBO J 2007; 26 (6): 1499–1510.

98. Williams KC, Coppolino MG. Phosphorylation of membrane type 1-matrix metalloproteinase (MT1-MMP) and its vesicle-associated membrane protein 7 (VAMP7) -dependent trafficking facilitate cell invasion and migration. J Biol Chem 2011; 286 (50): 43405–43416. doi: 10.1074/jbc.M111.297069.

99. Barbarin A, Frade R. Procathepsin L secretion, which triggers tumour progression, is regulated by Rab4a in human melanoma cells. Biochem J 2011; 437 (1): 97–107. doi: 10.1042/BJ20110361.

100. Steffan JJ, Dykes SS, Coleman DT et al. Supporting a role for the GTPase Rab7 in prostate cancer progression. PLoS One 2014; 9 (2): e87882. doi: 10.1371/journal.pone.0087882.

101. Hendrix A, Braems G, Bracke M et al. The secretory small GTPase Rab27B as a marker for breast cancer progression. Oncotarget 2010; 1 (4): 304–308.

102. Young J, Menetrey J, Goud B. RAB6C is a retrogene that encodes a centrosomal protein involved in cell cycle progression. J Mol Biol 2010; 397 (1): 69–88. doi: 10.1016/j.jmb.2010.01.009.

103. Pellinen T, Tuomi S, Arjonen A et al. Integrin trafficking regulated by Rab21 is necessary for cytokinesis. Dev Cell 2008; 15 (3): 371–385. doi: 10.1016/j.devcel.2008.08.001.

104. Ferrandiz-Huertas C, Fernandez-Carvajal A, Ferrer- -Montiel A. Rab4 interacts with the human P-glycoprotein and modulates its surface expression in multidrug resistant K562 cells. Int J Cancer 2011; 128 (1): 192–205. doi: 10.1002/ijc.25310.

105. Shen DW, Gottesman MM. RAB8 enhances TMEM205-mediated cisplatin resistance. Pharm Res 2012; 29 (3): 643–650. doi: 10.1007/s11095-011-0562-y.

106. Pei L, Peng Y, Yang Y et al. PRC17, a novel oncogene encoding a Rab GTPase-activating protein, is amplified in prostate cancer. Cancer Res 2002; 62 (19): 5420–5424.

107. Sato N, Koinuma J, Ito T et al. Activation of an oncogenic TBC1D7 (TBC1 domain family, member 7) protein in pulmonary carcinogenesis. Genes Chromosomes Cancer 2010; 49 (4): 353–367. doi: 10.1002/gcc.20747.

108. Chamberlain MD, Chan T, Oberg JC et al. Disrupted RabGAP function of the p85 subunit of phosphatidylinositol 3-kinase results in cell transformation. J Biol Chem 2008; 283 (23): 15861–15868. doi: 10.1074/jbc.M800941200.

109. Jenkins D, Seelow D, Jehee FS et al. RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. Am J Hum Genet 2007; 80 (6): 1162–1170.

Štítky
Paediatric clinical oncology Surgery Clinical oncology

Článok vyšiel v časopise

Clinical Oncology

Číslo Supplementum 4

2016 Číslo Supplementum 4
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#