Rab25 and RCP in cancer progression

  • Kyung Hwa Cho
  • Hoi Young LeeEmail author


Cancer invasion and metastasis is the crucial cause of death for most cancer patients. Endosome recycling of receptors for growth factors and adhesion molecules to the plasma membrane prevents them from degradation at the inside of the lysosome and recapitulates their functions, leading to major causativeness of cancer progression. Rab25 belongs to Rab-GTPase family and implicated in cancer progression in a context-dependent manner. Identified as a binding partner of Rab25, Rab coupling protein (RCP) augments cancer invasion and metastasis. In the present review, we document recent progress in Rab25- and RCP-induced cancer progression. In addition, we raise several questions should be answered for better understanding how endosome recycling by Rab25 and RCP influences cancer progression. Lastly, we update the potential therapeutic armaments to regulate Rab protein-induced endosome recycling for this deadly disease.


Endosome recycling Rab protein Rab25 Rab coupling protein Cancer progression 



Rab coupling protein


Receptor tyrosine kinase


Epidermal growth factor receptor


Transforming growth factor


Phosphoinositide 3-kinase


Guanine nucleotide exchange factor


GTPase-activating protein


Epithelial mesenchymal transition


DNA methyltransferases


Sirtuin 1


Triple-negative breast cancer


Vascular endothelial growth factor


Intracellular channel protein 3


Chloride intracellular channel protein 3


Rab11 family of interacting proteins


Rab binding domain


Non-small cell lung carcinoma


Estrogen receptor


Phosphatidic acid


Diacylglycerol kinase alpha




Mesenchymal–epithelial transition


WASP-interacting protein


Yes-associated protein


Rab geranylgeranyl transferase


Small interfering RNAs





This study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology [NRF-2017R1E1A1A01074091, 2017R1A2B4007361].

Compliance with ethical standards

Conflict of interest

The authors declare no conflict interest.


  1. Agarwal R, Jurisica I, Mills GB, Cheng KW (2009) The emerging role of the RAB25 small GTPase in cancer. Traffic 10:1561–1568CrossRefPubMedPubMedCentralGoogle Scholar
  2. Agola JO, Jim PA, Ward HH, Basuray S, Wandinger-Ness A (2011) Rab GTPases as regulators of endocytosis, targets of disease and therapeutic opportunities. Clin Genet 80:305–318CrossRefPubMedPubMedCentralGoogle Scholar
  3. Agola JO, Hong L, Surviladze Z, Ursu O, Waller A, Strouse JJ, Simpson DS, Schroeder CE, Oprea TI, Golden JE, Aube J, Buranda T, Sklar LA, Wandinger-Ness A (2012) A competitive nucleotide binding inhibitor: in vitro characterization of Rab7 GTPase inhibition. ACS Chem Biol 7:1095–1108CrossRefPubMedPubMedCentralGoogle Scholar
  4. Alonso-Curbelo D, Riveiro-Falkenbach E, Perez-Guijarro E, Cifdaloz M, Karras P, Osterloh L, Megias D, Canon E, Calvo TG, Olmeda D, Gomez-Lopez G, Grana O, Sanchez-Arevalo Lobo VJ, Pisano DG, Wang HW, Ortiz-Romero P, Tormo D, Hoek K, Rodriguez-Peralto JL, Joyce JA, Soengas MS (2014) RAB7 controls melanoma progression by exploiting a lineage-specific wiring of the endolysosomal pathway. Cancer Cell 26:61–76CrossRefPubMedGoogle Scholar
  5. Amornphimoltham P, Rechache K, Thompson J, Masedunskas A, Leelahavanichkul K, Patel V, Molinolo A, Gutkind JS, Weigert R (2013) Rab25 regulates invasion and metastasis in head and neck cancer. Clin Cancer Res 19:1375–1388CrossRefPubMedPubMedCentralGoogle Scholar
  6. Balsara BR, Sonoda G, Du Manoir S, Siegfried JM, Gabrielson E, Testa JR (1997) Comparative genomic hybridization analysis detects frequent, often high-level, overrepresentation of DNA sequences at 3q, 5p, 7p, and 8q in human non-small cell lung carcinomas. Cancer Res 57:2116–2120PubMedPubMedCentralGoogle Scholar
  7. Boucrot E, Ferreira AP, Almeida-Souza L, Debard S, Vallis Y, Howard G, Bertot L, Sauvonnet N, Mcmahon HT (2015) Endophilin marks and controls a clathrin-independent endocytic pathway. Nature 517:460–465CrossRefPubMedGoogle Scholar
  8. Boulay PL, Mitchell L, Turpin J, Huot-Marchand JE, Lavoie C, Sanguin-Gendreau V, Jones L, Mitra S, Livingstone JM, Campbell S, Hallett M, Mills GB, Park M, Chodosh L, Strathdee D, Norman JC, Muller WJ (2016) Rab11-FIP1C is a critical negative regulator in ErbB2-mediated mammary tumor progression. Cancer Res 76:2662–2674CrossRefPubMedPubMedCentralGoogle Scholar
  9. Bridgewater RE, Norman JC, Caswell PT (2012) Integrin trafficking at a glance. J Cell Sci 125:3695–3701CrossRefPubMedPubMedCentralGoogle Scholar
  10. Cao C, Lu C, Xu J, Zhang J, Li M (2013) Expression of Rab25 correlates with the invasion and metastasis of gastric cancer. Chin J Cancer Res 25:192–199PubMedPubMedCentralGoogle Scholar
  11. Casanova JE, Wang X, Kumar R, Bhartur SG, Navarre J, Woodrum JE, Altschuler Y, Ray GS, Goldenring JR (1999) Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells. Mol Biol Cell 10:47–61CrossRefPubMedPubMedCentralGoogle Scholar
  12. Caswell PT, Spence HJ, Parsons M, White DP, Clark K, Cheng KW, Mills GB, Humphries MJ, Messent AJ, Anderson KI, Mccaffrey MW, Ozanne BW, Norman JC (2007) Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments. Dev Cell 13:496–510CrossRefPubMedGoogle Scholar
  13. Caswell PT, Chan M, Lindsay AJ, Mccaffrey MW, Boettiger D, Norman JC (2008) Rab-coupling protein coordinates recycling of alpha5beta1 integrin and EGFR1 to promote cell migration in 3D microenvironments. J Cell Biol 183:143–155CrossRefPubMedPubMedCentralGoogle Scholar
  14. Caswell PT, Vadrevu S, Norman JC (2009) Integrins: masters and slaves of endocytic transport. Nat Rev Mol Cell Biol 10:843–853CrossRefPubMedGoogle Scholar
  15. Chano T, Avnet S (2018) RAB39A: a Rab small GTPase with a prominent role in cancer stemness. J Biochem 164:9–14CrossRefPubMedGoogle Scholar
  16. Cheng KW, Lahad JP, Kuo WL, Lapuk A, Yamada K, Auersperg N, Liu J, Smith-Mccune K, Lu KH, Fishman D, Gray JW, Mills GB (2004a) The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med 10:1251–1256CrossRefPubMedPubMedCentralGoogle Scholar
  17. Cheng KW, Lahad JP, Kuo WL, Lapuk A, Yamada K, Auersperg N, Liu J, Smith-Mccune K, Lu KH, Fishman D, Gray JW, Mills GB (2004b) The RAB25 small GTPase determines aggressiveness of ovarian and breast cancers. Nat Med 10:1251–1256CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cheng JM, Ding M, Aribi A, Shah P, Rao K (2006) Loss of RAB25 expression in breast cancer. Int J Cancer 118:2957–2964CrossRefPubMedGoogle Scholar
  19. Cheng JM, Volk L, Janaki DK, Vyakaranam S, Ran S, Rao KA (2010) Tumor suppressor function of Rab25 in triple-negative breast cancer. Int J Cancer 126:2799–2812PubMedGoogle Scholar
  20. Cheng KW, Agarwal R, Mitra S, Lee JS, Carey M, Gray JW, Mills GB (2012) Rab25 increases cellular ATP and glycogen stores protecting cancer cells from bioenergetic stress. EMBO Mol Med 4:125–141CrossRefPubMedPubMedCentralGoogle Scholar
  21. Choe SR, Kim YN, Park CG, Cho KH, Cho DY, Lee HY (2018) RCP induces FAK phosphorylation and ovarian cancer cell invasion with inhibition by curcumin. Exp Mol Med 50:52CrossRefPubMedPubMedCentralGoogle Scholar
  22. Chua CE, Tang BL (2015) The role of the small GTPase Rab31 in cancer. J Cell Mol Med 19:1–10CrossRefPubMedGoogle Scholar
  23. Clausen MJ, Melchers LJ, Mastik MF, Slagter-Menkema L, Groen HJ, Laan BF, Van Criekinge W, De Meyer T, Denil S, Van Der Vegt B, Wisman GB, Roodenburg JL, Schuuring E (2016) RAB25 expression is epigenetically downregulated in oral and oropharyngeal squamous cell carcinoma with lymph node metastasis. Epigenetics 11:653–663CrossRefPubMedPubMedCentralGoogle Scholar
  24. Coffill CR, Muller PA, Oh HK, Neo SP, Hogue KA, Cheok CF, Vousden KH, Lane DP, Blackstock WP, Gunaratne J (2012) Mutant p53 interactome identifies nardilysin as a p53R273H-specific binding partner that promotes invasion. EMBO Rep 13:638–644CrossRefPubMedPubMedCentralGoogle Scholar
  25. Court H, Ahearn IM, Amoyel M, Bach EA, Philips MR (2017) Regulation of NOTCH signaling by RAB7 and RAB8 requires carboxyl methylation by ICMT. J Cell Biol 216:4165–4182CrossRefPubMedPubMedCentralGoogle Scholar
  26. Coxon FP, Helfrich MH, Larijani B, Muzylak M, Dunford JE, Marshall D, Mckinnon AD, Nesbitt SA, Horton MA, Seabra MC, Ebetino FH, Rogers MJ (2001) Identification of a novel phosphonocarboxylate inhibitor of Rab geranylgeranyl transferase that specifically prevents Rab prenylation in osteoclasts and macrophages. J Biol Chem 276:48213–48222CrossRefPubMedGoogle Scholar
  27. Dai Y, Liu Y, Huang D, Yu C, Cai G, Pi L, Ren C, Chen GZ, Tian Y, Zhang X (2012) Increased expression of Rab coupling protein in squamous cell carcinoma of the head and neck and its clinical significance. Oncol Lett 3:1231–1236CrossRefPubMedPubMedCentralGoogle Scholar
  28. Deraeve C, Guo Z, Bon RS, Blankenfeldt W, Dilucrezia R, Wolf A, Menninger S, Stigter EA, Wetzel S, Choidas A, Alexandrov K, Waldmann H, Goody RS, Wu YW (2012) Psoromic acid is a selective and covalent Rab-prenylation inhibitor targeting autoinhibited RabGGTase. J Am Chem Soc 134:7384–7391CrossRefPubMedGoogle Scholar
  29. Ding B, Cui B, Gao M, Li Z, Xu C, Fan S, He W (2017) Knockdown of ras-related protein 25 (Rab25) inhibits the in vitro cytotoxicity and in vivo antitumor activity of human glioblastoma multiforme cells. Oncol Res 25:331–340CrossRefPubMedGoogle Scholar
  30. Dozynkiewicz MA, Jamieson NB, Macpherson I, Grindlay J, Van Den Berghe PV, Von Thun A, Morton JP, Gourley C, Timpson P, Nixon C, Mckay CJ, Carter R, Strachan D, Anderson K, Sansom OJ, Caswell PT, Norman JC (2012) Rab25 and CLIC3 collaborate to promote integrin recycling from late endosomes/lysosomes and drive cancer progression. Dev Cell 22:131–145CrossRefPubMedPubMedCentralGoogle Scholar
  31. Edinger AL, Cinalli RM, Thompson CB (2003) Rab7 prevents growth factor-independent survival by inhibiting cell-autonomous nutrient transporter expression. Dev Cell 5:571–582CrossRefPubMedGoogle Scholar
  32. Escoll M, Gargini R, Cuadrado A, Anton IM, Wandosell F (2017) Mutant p53 oncogenic functions in cancer stem cells are regulated by WIP through YAP/TAZ. Oncogene 36:3515–3527CrossRefPubMedGoogle Scholar
  33. Fukui K, Tamura S, Wada A, Kamada Y, Igura T, Kiso S, Hayashi N (2007) Expression of Rab5a in hepatocellular carcinoma: possible involvement in epidermal growth factor signaling. Hepatol Res 37:957–965CrossRefPubMedGoogle Scholar
  34. Geng D, Zhao W, Feng Y, Liu J (2016) Overexpression of Rab25 promotes hepatocellular carcinoma cell proliferation and invasion. Tumour Biol 37:7713–7718CrossRefPubMedGoogle Scholar
  35. Goldenring JR (2013) A central role for vesicle trafficking in epithelial neoplasia: intracellular highways to carcinogenesis. Nat Rev Cancer 13:813–820CrossRefPubMedPubMedCentralGoogle Scholar
  36. Goldenring JR, Shen KR, Vaughan HD, Modlin IM (1993) Identification of a small GTP-binding protein, Rab25, expressed in the gastrointestinal mucosa, kidney, and lung. J Biol Chem 268:18419–18422PubMedGoogle Scholar
  37. Gu Y, Zou YM, Lei D, Huang Y, Li W, Mo Z, Hu Y (2017) Promoter DNA methylation analysis reveals a novel diagnostic CpG-based biomarker and RAB25 hypermethylation in clear cell renel cell carcinoma. Sci Rep 7:14200CrossRefPubMedPubMedCentralGoogle Scholar
  38. Guerra F, and Bucci C (2016) Multiple roles of the small GTPase Rab7. Cells 5Google Scholar
  39. Gundry C, Marco S, Rainero E, Miller B, Dornier E, Mitchell L, Caswell PT, Campbell AD, Hogeweg A, Sansom OJ, Morton JP, Norman JC (2017) Phosphorylation of Rab-coupling protein by LMTK3 controls Rab14-dependent EphA2 trafficking to promote cell:cell repulsion. Nat Commun 8:14646CrossRefPubMedPubMedCentralGoogle Scholar
  40. Hales CM, Griner R, Hobdy-Henderson KC, Dorn MC, Hardy D, Kumar R, Navarre J, Chan EK, Lapierre LA, Goldenring JR (2001) Identification and characterization of a family of Rab11-interacting proteins. J Biol Chem 276:39067–39075CrossRefPubMedPubMedCentralGoogle Scholar
  41. Henriksen L, Grandal MV, Knudsen SL, Van Deurs B, Grovdal LM (2013) Internalization mechanisms of the epidermal growth factor receptor after activation with different ligands. PLoS ONE 8:e58148CrossRefPubMedPubMedCentralGoogle Scholar
  42. Hong L, Guo Y, Basuray S, Agola JO, Romero E, Simpson DS, Schroeder CE, Simons P, Waller A, Garcia M, Carter M, Ursu O, Gouveia K, Golden JE, Aube J, Wandinger-Ness A, Sklar LA (2015) A Pan-GTPase Inhibitor as a Molecular Probe. PLoS ONE 10:e0134317CrossRefPubMedPubMedCentralGoogle Scholar
  43. Hu C, Chen B, Zhou Y, Shan Y (2017) High expression of Rab25 contributes to malignant phenotypes and biochemical recurrence in patients with prostate cancer after radical prostatectomy. Cancer Cell Int 17:45CrossRefPubMedPubMedCentralGoogle Scholar
  44. Hung MC, Yang R, Sun Y (2016) Powering tumor metastasis with recycled fuel. Cancer Cell 30:374–375CrossRefPubMedGoogle Scholar
  45. Hwang MH, Cho KH, Jeong KJ, Park YY, Kim JM, Yu SL, Park CG, Mills GB, Lee HY (2017) RCP induces Slug expression and cancer cell invasion by stabilizing beta1 integrin. Oncogene 36:1102–1111CrossRefPubMedGoogle Scholar
  46. Jacquemet G, Green DM, Bridgewater RE, Von Kriegsheim A, Humphries MJ, Norman JC, Caswell PT (2013) RCP-driven alpha5beta1 recycling suppresses Rac and promotes RhoA activity via the RacGAP1-IQGAP1 complex. J Cell Biol 202:917–935CrossRefPubMedPubMedCentralGoogle Scholar
  47. Jeong BY, Cho KH, Jeong KJ, Park YY, Kim JM, Rha SY, Park CG, Mills GB, Cheong JH, Lee HY (2018) Rab25 augments cancer cell invasiveness through a beta1 integrin/EGFR/VEGF-A/Snail signaling axis and expression of fascin. Exp Mol Med 50:e435CrossRefPubMedPubMedCentralGoogle Scholar
  48. Jian Q, Miao Y, Tang L, Huang M, Yang Y, Ba W, Liu Y, Chi S, Li C (2016) Rab23 promotes squamous cell carcinoma cell migration and invasion via integrin beta1/Rac1 pathway. Oncotarget 7:5342–5352PubMedGoogle Scholar
  49. Jo U, Park KH, Whang YM, Sung JS, Won NH, Park JK, Kim YH (2014) EGFR endocytosis is a novel therapeutic target in lung cancer with wild-type EGFR. Oncotarget 5:1265–1278PubMedPubMedCentralGoogle Scholar
  50. Kessler D, Gruen GC, Heider D, Morgner J, Reis H, Schmid KW, Jendrossek V (2012) The action of small GTPases Rab11 and Rab25 in vesicle trafficking during cell migration. Cell Physiol Biochem 29:647–656CrossRefPubMedGoogle Scholar
  51. Kikuchi M, Yamashita K, Waraya M, Minatani N, Ushiku H, Kojo K, Ema A, Kosaka Y, Katoh H, Sengoku N, Enomoto T, Tanino H, Sawanobori M, Watanabe M (2016) Epigenetic regulation of ZEB1-RAB25/ESRP1 axis plays a critical role in phenylbutyrate treatment-resistant breast cancer. Oncotarget 7:1741–1753CrossRefPubMedGoogle Scholar
  52. Kiral FR, Kohrs FE, Jin EJ, Hiesinger PR (2018) Rab GTPases and membrane trafficking in neurodegeneration. Curr Biol 28:R471–R486CrossRefPubMedPubMedCentralGoogle Scholar
  53. Kou X, Yang Y, Jiang X, Liu H, Sun F, Wang X, Liu L, Lin Z, Jiang L (2017) Vorinostat and Simvastatin have synergistic effects on triple-negative breast cancer cells via abrogating Rab7 prenylation. Eur J Pharmacol 813:161–171CrossRefPubMedGoogle Scholar
  54. Lackner MR, Kindt RM, Carroll PM, Brown K, Cancilla MR, Chen C, De Silva H, Franke Y, Guan B, Heuer T, Hung T, Keegan K, Lee JM, Manne V, O’brien C, Parry D, Perez-Villar JJ, Reddy RK, Xiao H, Zhan H, Cockett M, Plowman G, Fitzgerald K, Costa M, Ross-Macdonald P (2005) Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitors. Cancer Cell 7:325–336CrossRefPubMedGoogle Scholar
  55. Lanzetti L, Di Fiore PP (2017) Behind the scenes: endo/exocytosis in the acquisition of metastatic traits. Cancer Res 77:1813–1817CrossRefPubMedGoogle Scholar
  56. Li Y, Jia Q, Zhang Q, Wan Y (2015) Rab25 upregulation correlates with the proliferation, migration, and invasion of renal cell carcinoma. Biochem Biophys Res Commun 458:745–750CrossRefPubMedGoogle Scholar
  57. Lindsay AJ, Mccaffrey MW (2004) The C2 domains of the class I Rab11 family of interacting proteins target recycling vesicles to the plasma membrane. J Cell Sci 117:4365–4375CrossRefPubMedGoogle Scholar
  58. Lindsay AJ, Hendrick AG, Cantalupo G, Senic-Matuglia F, Goud B, Bucci C, Mccaffrey MW (2002) Rab coupling protein (RCP), a novel Rab4 and Rab11 effector protein. J Biol Chem 277:12190–12199CrossRefPubMedGoogle Scholar
  59. Liu L, Ding G (2014) Rab25 expression predicts poor prognosis in clear cell renal cell carcinoma. Exp Ther Med 8:1055–1058CrossRefPubMedPubMedCentralGoogle Scholar
  60. Liu Y, Zeng C, Bao N, Zhao J, Hu Y, Li C, Chi S (2015) Effect of Rab23 on the proliferation and apoptosis in breast cancer. Oncol Rep 34:1835–1844CrossRefPubMedGoogle Scholar
  61. Ma YF, Yang B, Li J, Zhang T, Guo JT, Chen L, Li M, Chu J, Liang CY, Liu Y (2015) Expression of Ras-related protein 25 predicts chemotherapy resistance and prognosis in advanced non-small cell lung cancer. Genet Mol Res 14:13998–14008CrossRefPubMedGoogle Scholar
  62. Macpherson IR, Rainero E, Mitchell LE, Van Den Berghe PV, Speirs C, Dozynkiewicz MA, Chaudhary S, Kalna G, Edwards J, Timpson P, Norman JC (2014) CLIC3 controls recycling of late endosomal MT1-MMP and dictates invasion and metastasis in breast cancer. J Cell Sci 127:3893–3901CrossRefPubMedGoogle Scholar
  63. Mafakheri S, Chadt A, Al-Hasani H (2018) Regulation of RabGAPs involved in insulin action. Biochem Soc Trans 46:683–690CrossRefPubMedGoogle Scholar
  64. Menard L, Floc’h N, Martin MJ, DaE Cross (2018) Reactivation of mutant-EGFR degradation through clathrin inhibition overcomes resistance to EGFR tyrosine kinase inhibitors. Cancer Res 78:3267–3279CrossRefPubMedGoogle Scholar
  65. Mills GB, Jurisica I, Yarden Y, Norman JC (2009) Genomic amplicons target vesicle recycling in breast cancer. J Clin Invest 119:2123–2127PubMedPubMedCentralGoogle Scholar
  66. Mitra S, Cheng KW, Mills GB (2012) Rab25 in cancer: a brief update. Biochem Soc Trans 40:1404–1408CrossRefPubMedPubMedCentralGoogle Scholar
  67. Mitra S, Federico L, Zhao W, Dennison J, Sarkar TR, Zhang F, Takiar V, Cheng KW, Mani S, Lee JS, Mills GB (2016) Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT. Oncotarget 7:40252–40265PubMedPubMedCentralGoogle Scholar
  68. Mitra S, Montgomery JE, Kolar MJ, Li G, Jeong KJ, Peng B, Verdine GL, Mills GB, Moellering RE (2017) Stapled peptide inhibitors of RAB25 target context-specific phenotypes in cancer. Nat Commun 8:660CrossRefPubMedPubMedCentralGoogle Scholar
  69. Mor O, Nativ O, Stein A, Novak L, Lehavi D, Shiboleth Y, Rozen A, Berent E, Brodsky L, Feinstein E, Rahav A, Morag K, Rothenstein D, Persi N, Mor Y, Skaliter R, Regev A (2003) Molecular analysis of transitional cell carcinoma using cDNA microarray. Oncogene 22:7702–7710CrossRefGoogle Scholar
  70. Muller PA, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S, Lukashchuk N, Gillespie DA, Ludwig RL, Gosselin P, Cromer A, Brugge JS, Sansom OJ, Norman JC, Vousden KH (2009) Mutant p53 drives invasion by promoting integrin recycling. Cell 139:1327–1341CrossRefPubMedGoogle Scholar
  71. Muller PA, Trinidad AG, Timpson P, Morton JP, Zanivan S, Van Den Berghe PV, Nixon C, Karim SA, Caswell PT, Noll JE, Coffill CR, Lane DP, Sansom OJ, Neilsen PM, Norman JC, Vousden KH (2013) Mutant p53 enhances MET trafficking and signalling to drive cell scattering and invasion. Oncogene 32:1252–1265CrossRefPubMedGoogle Scholar
  72. Nam KT, Lee HJ, Smith JJ, Lapierre LA, Kamath VP, Chen X, Aronow BJ, Yeatman TJ, Bhartur SG, Calhoun BC, Condie B, Manley NR, Beauchamp RD, Coffey RJ, Goldenring JR (2010) Loss of Rab25 promotes the development of intestinal neoplasia in mice and is associated with human colorectal adenocarcinomas. J Clin Invest 120:840–849CrossRefPubMedPubMedCentralGoogle Scholar
  73. Natrajan R, Williams RD, Hing SN, Mackay A, Reis-Filho JS, Fenwick K, Iravani M, Valgeirsson H, Grigoriadis A, Langford CF, Dovey O, Gregory SG, Weber BL, Ashworth A, Grundy PE, Pritchard-Jones K, Jones C (2006) Array CGH profiling of favourable histology Wilms tumours reveals novel gains and losses associated with relapse. J Pathol 210:49–58CrossRefPubMedGoogle Scholar
  74. Paul NR, Allen JL, Chapman A, Morlan-Mairal M, Zindy E, Jacquemet G, Fernandez Del Ama L, Ferizovic N, Green DM, Howe JD, Ehler E, Hurlstone A, Caswell PT (2015) alpha5beta1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3. J Cell Biol 210:1013–1031CrossRefPubMedPubMedCentralGoogle Scholar
  75. Prekeris R, Klumperman J, Scheller RH (2000) A Rab11/Rip11 protein complex regulates apical membrane trafficking via recycling endosomes. Mol Cell 6:1437–1448CrossRefPubMedGoogle Scholar
  76. Qin X, Wang J, Wang X, Liu F, Jiang B, Zhang Y (2017) Targeting Rabs as a novel therapeutic strategy for cancer therapy. Drug Discov Today 22:1139–1147CrossRefPubMedGoogle Scholar
  77. Rainero E, Norman JC (2013) Late endosomal and lysosomal trafficking during integrin-mediated cell migration and invasion: cell matrix receptors are trafficked through the late endosomal pathway in a way that dictates how cells migrate. BioEssays 35:523–532CrossRefPubMedGoogle Scholar
  78. Rainero E, Caswell PT, Muller PA, Grindlay J, Mccaffrey MW, Zhang Q, Wakelam MJ, Vousden KH, Graziani A, Norman JC (2012) Diacylglycerol kinase alpha controls RCP-dependent integrin trafficking to promote invasive migration. J Cell Biol 196:277–295CrossRefPubMedPubMedCentralGoogle Scholar
  79. Roche J, Nasarre P, Gemmill R, Baldys A, Pontis J, Korch C, Guilhot J, Ait-Si-Ali S, Drabkin H (2013) Global decrease of histone H3K27 acetylation in ZEB1-induced epithelial to mesenchymal transition in lung cancer cells. Cancers 5:334–356CrossRefPubMedPubMedCentralGoogle Scholar
  80. Shi F, Sottile J (2008) Caveolin-1-dependent beta1 integrin endocytosis is a critical regulator of fibronectin turnover. J Cell Sci 121:2360–2371CrossRefPubMedPubMedCentralGoogle Scholar
  81. Shinde SR, Maddika S (2016) PTEN modulates EGFR late endocytic trafficking and degradation by dephosphorylating Rab7. Nat Commun 7:10689CrossRefPubMedPubMedCentralGoogle Scholar
  82. Sigismund S, Argenzio E, Tosoni D, Cavallaro E, Polo S, Di Fiore PP (2008) Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation. Dev Cell 15:209–219CrossRefPubMedGoogle Scholar
  83. Skrypek N, Bruneel K, Vandewalle C, De Smedt E, Soen B, Loret N, Taminau J, Goossens S, Vandamme N, Berx G (2018) ZEB2 stably represses RAB25 expression through epigenetic regulation by SIRT1 and DNMTs during epithelial-to-mesenchymal transition. Epigenetics Chromatin 11:70CrossRefPubMedPubMedCentralGoogle Scholar
  84. Steffan JJ, Cardelli JA (2010) Thiazolidinediones induce Rab7-RILP-MAPK-dependent juxtanuclear lysosome aggregation and reduce tumor cell invasion. Traffic 11:274–286CrossRefPubMedGoogle Scholar
  85. Steffan JJ, Dykes SS, Coleman DT, Adams LK, Rogers D, Carroll JL, Williams BJ, Cardelli JA (2014) Supporting a role for the GTPase Rab7 in prostate cancer progression. PLoS ONE 9:e87882CrossRefPubMedPubMedCentralGoogle Scholar
  86. Suwandittakul N, Reamtong O, Molee P, Maneewatchararangsri S, Sutherat M, Chaisri U, Wongkham S, Adisakwattana P (2017) Disruption of endocytic trafficking protein Rab7 impairs invasiveness of cholangiocarcinoma cells. Cancer Biomark 20:255–266CrossRefPubMedGoogle Scholar
  87. Tang BL (2010) Is Rab25 a tumor promoter or suppressor–context dependency on RCP status? Tumour Biol 31:359–361CrossRefPubMedGoogle Scholar
  88. Tang CT, Liang Q, Yang L, Lin XL, Wu S, Chen Y, Zhang XT, Gao YJ, Gezz (2018) RAB31 targeted by MiR-30c-2-3p regulates the GLI1 signaling pathway, affecting gastric cancer cell proliferation and apoptosis. Front Oncol 8:554CrossRefPubMedPubMedCentralGoogle Scholar
  89. Tomas A, Futter CE, Eden ER (2014) EGF receptor trafficking: consequences for signaling and cancer. Trends Cell Biol 24:26–34CrossRefPubMedPubMedCentralGoogle Scholar
  90. Tong M, Chan KW, Bao JY, Wong KY, Chen JN, Kwan PS, Tang KH, Fu L, Qin YR, Lok S, Guan XY, Ma S (2012) Rab25 is a tumor suppressor gene with antiangiogenic and anti-invasive activities in esophageal squamous cell carcinoma. Cancer Res 72:6024–6035CrossRefPubMedGoogle Scholar
  91. Tsai CH, Cheng HC, Wang YS, Lin P, Jen J, Kuo IY, Chang YH, Liao PC, Chen RH, Yuan WC, Hsu HS, Yang MH, Hsu MT, Wu CY, Wang YC (2014) Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis. Nat Commun 5:4804CrossRefPubMedGoogle Scholar
  92. Tzeng HT, Wang YC (2016) Rab-mediated vesicle trafficking in cancer. J Biomed Sci 23:70CrossRefPubMedPubMedCentralGoogle Scholar
  93. Tzeng HT, Tsai CH, Yen YT, Cheng HC, Chen YC, Pu SW, Wang YS, Shan YS, Tseng YL, Su WC, Lai WW, Wu LW, Wang YC (2017) Dysregulation of Rab37-mediated cross-talk between cancer cells and endothelial cells via thrombospondin-1 promotes tumor neovasculature and metastasis. Clin Cancer Res 23:2335–2345CrossRefPubMedGoogle Scholar
  94. Wang T, Zhang M, Ma Z, Guo K, Tergaonkar V, Zeng Q, Hong W (2012) A role of Rab7 in stabilizing EGFR-Her2 and in sustaining Akt survival signal. J Cell Physiol 227:2788–2797CrossRefPubMedGoogle Scholar
  95. Wang M, Dong Q, Wang Y (2016) Rab23 is overexpressed in human astrocytoma and promotes cell migration and invasion through regulation of Rac1. Tumour Biol 37:11049–11055CrossRefPubMedGoogle Scholar
  96. Wang S, Hu C, Wu F, He S (2017a) Rab25 GTPase: functional roles in cancer. Oncotarget 8:64591–64599PubMedPubMedCentralGoogle Scholar
  97. Wang W, Zhang H, Liu S, Kim CK, Xu Y, Hurley LA, Nishikawa R, Nagane M, Hu B, Stegh AH, Cheng SY, Cheng C (2017b) Internalized CD44s splice isoform attenuates EGFR degradation by targeting Rab7A. Proc Natl Acad Sci USA 114:8366–8371CrossRefPubMedGoogle Scholar
  98. Wheeler DB, Zoncu R, Root DE, Sabatini DM, Sawyers CL (2015) Identification of an oncogenic RAB protein. Science 350:211–217CrossRefPubMedPubMedCentralGoogle Scholar
  99. Williams KC, Coppolino MG (2011) 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 286:43405–43416CrossRefPubMedPubMedCentralGoogle Scholar
  100. Wrzeszczynski KO, Varadan V, Byrnes J, Lum E, Kamalakaran S, Levine DA, Dimitrova N, Zhang MQ, Lucito R (2011) Identification of tumor suppressors and oncogenes from genomic and epigenetic features in ovarian cancer. PLoS ONE 6:e28503CrossRefPubMedPubMedCentralGoogle Scholar
  101. Yang PS, Yin PH, Tseng LM, Yang CH, Hsu CY, Lee MY, Horng CF, Chi CW (2011) Rab5A is associated with axillary lymph node metastasis in breast cancer patients. Cancer Sci 102:2172–2178CrossRefPubMedGoogle Scholar
  102. Yin C, Mou Q, Pan X, Zhang G, Li H, Sun Y (2018) MiR-577 suppresses epithelial-mesenchymal transition and metastasis of breast cancer by targeting Rab25. Thorac Cancer 9:472–479CrossRefPubMedPubMedCentralGoogle Scholar
  103. Yu L, Hui-Chen F, Chen Y, Zou R, Yan S, Chun-Xiang L, Wu-Ru W, Li P (1999) Differential expression of RAB5A in human lung adenocarcinoma cells with different metastasis potential. Clin Exp Metastasis 17:213–219CrossRefPubMedGoogle Scholar
  104. Yu MH, Luo Y, Qin SL, Zhong M (2015) Increased expression of Rab5A predicts metastasis and poor prognosis in colorectal cancer patients. Int J Clin Exp Pathol 8:6974–6980PubMedPubMedCentralGoogle Scholar
  105. Zhang J, Liu X, Datta A, Govindarajan K, Tam WL, Han J, George J, Wong C, Ramnarayanan K, Phua TY, Leong WY, Chan YS, Palanisamy N, Liu ET, Karuturi KM, Lim B, Miller LD (2009) RCP is a human breast cancer-promoting gene with Ras-activating function. J Clin Invest 119:2171–2183PubMedPubMedCentralGoogle Scholar
  106. Zhang J, Wei J, Lu J, Tong Z, Liao B, Yu B, Zheng F, Huang X, Chen Z, Fang Y, Li B, Chen W, Xie D, Luo J (2013) Overexpression of Rab25 contributes to metastasis of bladder cancer through induction of epithelial-mesenchymal transition and activation of Akt/GSK-3beta/Snail signaling. Carcinogenesis 34:2401–2408CrossRefPubMedGoogle Scholar
  107. Zhang D, Lu C, Ai H (2017) Rab5a is overexpressed in oral cancer and promotes invasion through ERK/MMP signaling. Mol Med Rep 16:4569–4576CrossRefPubMedPubMedCentralGoogle Scholar
  108. Zhou Y, Wu B, Li JH, Nan G, Jiang JL, Chen ZN (2017) Rab22a enhances CD147 recycling and is required for lung cancer cell migration and invasion. Exp Cell Res 357:9–16CrossRefPubMedGoogle Scholar
  109. Zhu H, Liang Z, Li G (2009) Rabex-5 is a Rab22 effector and mediates a Rab22-Rab5 signaling cascade in endocytosis. Mol Biol Cell 20:4720–4729CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.Department of Pharmacology, College of MedicineKonyang UniversityDaejeonRepublic of Korea

Personalised recommendations