CD34家族成員包含CD34、PODXL與PODXL2，因為表達於造血祖細胞與內皮細胞中而被廣泛地用於當作造血幹細胞與血管相關組織的指標蛋白。過去文獻指出家族蛋白中PODXL在多種惡性腫瘤中是高度表達，例如乳癌、肺癌、大腸癌等，並且往往造成病人不良的預後。PODXL會透過促使癌細胞的『侵襲偽足』形成、癌細胞進行上皮間質轉化，進而促使腫瘤遷移和侵襲。PODXL的表達還與乳癌和結腸癌的化療耐受性和腫瘤幹細胞的幹性有關。然而同一家族中的PODXL2在癌症中的角色則尚不清楚。為了瞭解PODXL2是如何促進腫瘤進展，我們首先藉由生物資訊的方式進行觀察並搜集資料。在Oncomine癌症微陣列數據庫與The Human Protein Atlas資料庫的中分析顯示了PODXL2的基因與蛋白質在乳癌中是顯著表達。接著藉由Kaplan-Meier plotter的分析顯示出當PODXL2過度表達會與乳癌病患不良的預後有關。綜合生物資訊的分析，我們推測PODXL2可能在乳癌中扮演著致癌基因的角色。為了探討PODXL2在乳癌中的功能，我們提取了癌細胞系百科全書數據庫(CCLE)中乳癌細胞株對於PODXL2的表達數據。本研究的第二個目的是利用shRNA沉默技術研究PODXL2的功能。我們首先藉由PODLX2-shRNA在BT474細胞中沉默PODXL2表現，接著藉由MTT方式觀察細胞短期增生能力，結果是沒有影響的。然而在傷口癒合細胞爬行試驗中發現當我們在BT474細胞中下調PODXL2會造成細胞爬行能力下降，同時Rac1、磷酸化的Akt (S473)與paxillin (pY31)表現量也隨之下降。另一方面我們在MCF-7細胞中提升PODXL2表達後發現相對於控制組細胞來說會具有較高的細胞爬行能力。我們同時也去觀察幹細胞的指標蛋白Nanog和Oct-4與乳癌幹細胞指標蛋白ALDH1的蛋白質表現量，同樣在抑制了PODXL2後Nanog與Oct-4的表現也隨之下降。綜合以上數據，關於PODXL2在乳癌中對於細胞爬行及幹細胞可能扮演的角色是值得進一步去探討的。

The CD34 family, CD34, PODXL and PODXL2, are Type-I transmembrane sialomucins and markers of hematopoietic stem cells (HSCs) and vascular associated tissues, which are expressed on endothelial cells and hematopoietic precursors. Overexpression of PODXL is correlated with poor survival in several malignancies. The effects of PODXL have been associated with invadopodia formation as well as promote epithelial–mesenchymal transition (EMT) and tumor migration and invasion in breast and lung cancers. Furthermore, expression of PODXL has been associated with the stem cell signature and chemotherapy resistance in breast and colon cancers. However, the role for PODXL2 in cancer remains largely unclear. To understand the contribution of PODXL2 to tumor progression, a detailed analysis of their role in breast cancer should be explored. The first aim of the present study was to evaluate the expression of PODXL2 protein and its correlation with the clinical outcome of patients with cancer. Analysis of the Oncomine cancer microarray database revealed that PODXL2 gene expression was significantly increased in breast carcinoma. Kaplan-Meier analysis showed that overexpression of PODXL2 was associated with poor prognosis. Thus, we hypothesized that PODXL2 may play an oncogenic role in breast cancer. In order to examine the effect of PODXL2, we extracted data on PODXL2 expression from CCLE databases for breast cancer cell lines BT474 and MCF7. The second aim of this study is to study the function of PODXL2 with shRNA silencing techniques. The short-term cell proliferation ability of the PODXL2-silencing BT474 cells was not altered by PODXL2 shRNA. However, the down-regulation of PODXL2 in BT474 cells by shRNAs decreased cell migration abilities and Rac1, phosphor-Akt (S473) and phosphor-paxillin (Y31) protein expression. Furthermore, the expression level of CSC markers Oct-4 and Nanog and breast CSC marker ALDH1 also decreased by PODXL2 shRNA. To confirm the effect of PODXL2 on cancer cell, this protein was ectopically expressed in the MCF-7 cells. Elevated PODXL2 protein expression resulted in a relatively high cell migration potential. According to the results above, the role of PODXL2 in cancer migration and stemness warrants further investigation.

1. Siegel RL, Miller KD and Jemal A. Cancer Statistics, 2017. CA Cancer J Clin.; 2017; 67(1):7-30.
2. Qian CN, Mei Y and Zhang J. Cancer metastasis: issues and challenges. Chinese Journal of Cancer; 2017; 36:38.
3. Esmatabadi MJ, Bakhshinejad B, Motlagh FM, Babashah S, Sadeghizadeh M. Therapeutic resistance and cancer recurrence mechanisms: Unfolding the story of tumour coming back. Journal of biosciences, 2016; 41(3):497-506.
4. O'Flaherty JD, Barr M, Fennell D, Richard D, Reynolds J, O'Leary J and O'Byrne K.The cancer stem-cell hypothesis: its emerging role in lung cancer biology and its relevance for future therapy. J Thorac Oncol. 2012; 7(12):1880-90.
5. Herrmann H, Sadovnik I, Cerny-Reiterer S, Rülicke T, Stefanzl G, Willmann M, Hoermann G, Bilban M, Blatt K, Herndlhofer S, Mayerhofer M, Streubel B, Sperr WR, Holyoake TL, Mannhalter C, Valent P. Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia. Blood, 2014; 123(25): 3951-62.
6. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature, 2004; 432(7015): 396-401.
7. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A, 2003; 100(7):3983-8.
8. Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, Soh BS, Sun LL, Tai BC, Nga ME, Bhakoo KK, Jayapal SR, Nichane M, Yu Q, Ahmed DA, Tan C, Sing WP, Tam J, Thirugananam A, Noghabi MS, Pang YH, Ang HS, Mitchell W, Robson P, Kaldis P, Soo RA, Swarup S, Lim EH, Lim B. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell, 2012; 148(1-2):259-72.
9. Kim WT, Ryu CJ. Cancer stem cell surface markers on normal stem cells. BMB Rep., 2017; 50(6):285-298.
10. O'Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature, 2007; 445(7123):106-10.
11. Chang JC. Cancer stem cells: Role in tumor growth, recurrence, metastasis, and treatment resistance. Medicine, 2016; 95(1 Suppl 1):S20-5.
12. Vazquez-Santillan K, Melendez-Zajgla J, Jimenez-Hernandez LE, Gaytan-Cervantes J, Muñoz-Galindo L, Piña-Sanchez P, Martinez-Ruiz G, Torres J, Garcia-Lopez P, Gonzalez-Torres C, Ruiz V, Avila-Moreno F, Velasco-Velazquez M, Perez-Tapia M, Maldonado V. NF-kappaΒ-inducing kinase regulates stem cell phenotype in breast cancer. Scientific reports, 2016; 6:37340.
13. Eskander RN and Tewari KS. Beyond angiogenesis blockade: targeted therapy for advanced cervical cancer. J Gynecol Oncol., 2014 ;25(3):249-59
14. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, Minden M, Paterson B, Caligiuri MA, Dick JE. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 1994; 367(6464):645-8.
15. Krause DS, Ito T, Fackler MJ, Smith OM, Collector MI, Sharkis SJ, May WS. Characterization of murine CD34, a marker for hematopoietic progenitor and stem cells. Blood, 1994; 84(3):691-701.
16. Cheng J, Baumhueter S, Cacalano G, Carver-Moore K, Thibodeaux H, Thomas R, Broxmeyer HE, Cooper S, Hague N, Moore M, Lasky LA. Hematopoietic defects in mice lacking the sialomucin CD34. Blood, 1996; 87(2):497-90.
17. Nielsen JS and McNagny KM. Novel functions of the CD34 family. Journal of Cell Science, 2008; 121(Pt 22):3683-92.
18. Doyonnas R, Kershaw DB, Duhme C, Merkens H, Chelliah S, Graf T, McNagny KM. Anuria, omphalocele, and perinatal lethality in mice lacking the CD34-related protein podocalyxin. J Exp Med., 2001; 194(1):13-27.
19. Sassetti, C, Van Zante, A. and Rosen, S. D. Identification of endoglycan, a member of the CD34/podocalyxin family of sialomucins. J. Biol. Chem., 2000; 275, 9001-9010.
20. Suda J, Sudo T, Ito M, Ohno N, Yamaguchi Y, Suda T. Two types of murine CD34 mRNA generated by alternative splicing. Blood, 1992; 79(9):2288-95.
21. Berenson RJ, Andrews RG, Bensinger WI, Kalamasz D, Knitter G, Buckner CD, Bernstein ID. Antigen CD34+ marrow cells engraft lethally irradiated baboons. J Clin Invest., 1988; 81(3):951-5.
22. Civin CI, Strauss LC, Brovall C, Fackler MJ, Schwartz JF, Shaper JH. Antigenic analysis of hematopoiesis. III. A hematopoietic progenitor cell surface antigen defined by a monoclonal antibody raised against KG-1a cells. J Immunol., 1984;133(1):157-65.
23. Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A. Concise Review: Evidence for CD34 as a Common Marker for Diverse Progenitors. Stem Cells, 2014; 32(6):1380-9.
24. Drew E, Merkens H, Chelliah S, Doyonnas R, McNagny KM. CD34 is a specific marker of mature murine mast cells. Exp Hematol., 2002; 30(10):1211-8.
25. Blanchet, Maltby S, Haddon DJ, Merkens H, Zbytnuik L, McNagny KM. CD34 facilitates the development of allergic asthma. Blood, 2007; 110(6):2005-12.
26. Baumheter S, Singer MS, Henzel W, Hemmerich S, Renz M, Rosen SD, Lasky LA. Binding of L-selectin to the vascular sialomucin CD34. Science, 1933; 262(5132):436-8.
27. Petri B and Bixel MG. Molecular events during leukocyte diapedesis. FEBS J., 2006; 273(19):4399-407.
28. Lam MCW. Expression and Distribution of Endoglycan on B cells. The University of British Columbia, 2002
29. Maenhout TM, Moreau E, Van Haute I, Desmet S, Deeren D. Minimal Coexpression of CD34+/CD56+ in Acute Promyelocytic Leukemia Is Associated With Relapse. Am J Clin Pathol., 2015; 144(2):347-51.
30. Maschio LB, Madallozo BB, Capellasso BA, Jardim BV, Moschetta MG, Jampietro J, Soares FA, Zuccari DA. Immunohistochemical investigation of the angiogenic proteins VEGF, HIF-1α and CD34 in invasive ductal carcinoma of the breast. Acta Histochem., 2014; 116(1):148-57.
31. Goldiş DS, Sferdian MF, Tarţă C, Fulger LO, Totolici BD, Neamţu C. Comparative analysis of microvessel density quantified through the immunohistochemistry expression of CD34 and CD105 in rectal cancer. Rom J Morphol Embryol., 2015; 56(2):419-24.
32. Miettinen A, Solin ML, Reivinen J, Juvonen E, Väisänen R, Holthöfer H. Podocalyxin in rat platelets and megakaryocytes. Am J Pathol., 1999 ;154(3):813-22.
33. Doyonnas R, Nielsen JS, Chelliah S, Drew E, Hara T, Miyajima A, McNagny KM. Podocalyxin is a CD34-related marker of murine hematopoietic stem cells and embryonic erythroid cells. Blood, 2005; 105(11):4170-8.
34. Schnabel E, Dekan G, Miettinen A, Farquhar MG. Biogenesis of podocalyxin--the major glomerular sialoglycoprotein--in the newborn rat kidney. Eur J Cell Biol., 1989; 48(2):313-26.
35. Kerjaschki D,Sharkey DJ, Farquhar MG. Identification and characterization of podocalyxin--the major sialoprotein of the renal glomerular epithelial cell. J Cell Biol., 1984; 98(4):1591-6.
36. Somasiri A, Nielsen JS, Makretsov N, McCoy ML, Prentice L, Gilks CB, Chia SK, Gelmon KA, Kershaw DB, Huntsman DG, McNagny KM, Roskelley CD. Overexpression of the anti-adhesin podocalyxin is an independent predictor of breast cancer progression. Cancer Res., 2004; 64(15):5068-73.
37. Cipollone JA, Graves ML, Köbel M, Kalloger SE, Poon T, Gilks CB, McNagny KM, Roskelley CD. The anti-adhesive mucin podocalyxin may help initiate the transperitoneal metastasis of high grade serous ovarian carcinoma. Clin Exp Metastasis. 2012; 29(3):239-52.
38. Koch LK, Zhou H, Ellinger J, Biermann K, Höller T, von Rücker A, Büttner R, Gütgemann I. Stem cell marker expression in small cell lung carcinoma and developing lung tissue. Hum Pathol., 2008; 39(11):1597-605.
39. Yu YP, Landsittel D, Jing L, Nelson J, Ren B, Liu L, McDonald C, Thomas R, Dhir R, Finkelstein S, Michalopoulos G, Becich M, Luo JH. Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy. J Clin Oncol. 2004; 22(14):2790-9.
40. Chen X, Higgins J, Cheung ST, Li R, Mason V, Montgomery K, Fan ST, van de Rijn M, So S. Novel endothelial cell markers in hepatocellular carcinoma. Mod Pathol., 2004; 17(10):1198-210.
41. Thomas SN, Schnaar RL, Konstantopoulos K. Podocalyxin-like protein is an E-/L-selectin ligand on colon carcinoma cells: comparative biochemical properties of selectin ligands in host and tumor cells. Am J Physiol Cell Physiol., 2009; 296(3):C505-13.
42. Taniuchi K, Furihata M, Naganuma S, Dabanaka K, Hanazaki K, Saibara T. Podocalyxin-like protein, linked to poor prognosis of pancreatic cancers, promotes cell invasion by binding to gelsolin. Cancer Sci., 2016; 107(10):1430-1442.
43. Mcnagny KM, Mccoll SR. et al. Podocalyxin in the Diagnosis and Treatment of Cancer. Advances in Cancer Management, 2012 January.
44. Lin CW, Sun MS, Liao MY, Chung CH, Chi YH, Chiou LT, Yu J, Lou KL, Wu HC. Podocalyxin-like 1 promotes invadopodia formation and metastasis through activation of Rac1/Cdc42/cortactin signaling in breast cancer cells. Carcinogenesis, 2014; 35(11):2425-35.
45. Sizemore S, Cicek M, Sizemore N, Ng KP, Casey G. Podocalyxin increases the aggressive phenotype of breast and prostate cancer cells in vitro through its interaction with ezrin. Cancer Res. 2007; 67(13):6183-91.
46. Kusumoto H, Shintani Y, Kanzaki R, Kawamura T, Funaki S, Minami M, Nagatomo I, Morii E, Okumura M. Podocalyxin influences malignant potential by controlling epithelial-mesenchymal transition in lung adenocarcinoma. Cancer Sci., 2017; 108(3):528-535.
47. Amo L, Tamayo-Orbegozo E, et al. Involvement of Platelet–Tumor Cell Interaction in Immune Evasion. Potential Role of Podocalyxin-Like Protein 1. Front Oncol. 2014; 4: 245.
48. Amo L, Tamayo-Orbegozo E, Maruri N, Buqué A, Solaun M, Riñón M, Arrieta A, Larrucea S. Podocalyxin-like protein 1 functions as an immunomodulatory molecule in breast cancer cells. Cancer Lett. 2015; 368(1):26-35.
49. Lee WY, Kuo CC, Lin BX, Cheng CH, Chen KC, Lin CW. Podocalyxin-Like Protein 1 Regulates TAZ Signaling and Stemness Properties in Colon Cancer. Int J Mol Sci., 2017; 18(10). pii: E2047.
50. Fieger CB, Sassetti CM, Rosen SD. Endoglycan, a member of the CD34 family, functions as an L-selectin ligand through modification with tyrosine sulfation and sialyl Lewis x. J Biol Chem., 2003; 278(30):27390-8.
51. Kerr SC, Fieger CB, Snapp KR, Rosen SD. Endoglycan, a member of the CD34 family of sialomucins, is a ligand for the vascular selectins. J Immunol. 2008; 181(2):1480-90.
52. Yang Z, Zimmerman SE, Tsunezumi J, Braitsch C, Trent C, Bryant DM, Cleaver O, González-Manchón C, Marciano DK. Role of CD34 family members in lumen formation in the developing kidney. Dev Biol., 2016; 418(1):66-74.
53. Hanna WM and Corkill M. Mucins in breast carcinoma. Hum Pathol., 1988; 19(1):11-4.
54. Nicolini A, Ferrari P, Rossi G. Mucins and Cytokeratins as Serum Tumor Markers in Breast Cancer. Mucins and Cytokeratins as Serum Tumor Markers in Breast Cancer. Adv Exp Med Biol. 2015; 867:197-225.
55. Perrais M, Pigny P, Buisine M-P, Porchet N, Aubert J-P, andSeuningen-Lempire IV. Aberrant expression of human mucin gene MUC5B in gastric carcinoma and cancer cells. Identification and regulation of a distal promoter. J Biol Chem., 2001; 276:15386–15396.
56. Song S, Byrd JC, Mazurek N, Liu K, Koo JS, Bresalier RS. Galectin-3 modulates MUC2 mucin expression in human colon cancer cells at the level of transcription via AP-1 activation. Gastroenterology, 2005; 129(5):1581-91.
57. Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer. 2009; 9(12):874-85.
58. Chen WC, Wang CY, Hung YH, Weng TY, Yen MC, Lai MD. Systematic Analysis of Gene Expression Alterations and Clinical Outcomes for Long-Chain Acyl-Coenzyme A Synthetase Family in Cancer. PLoS One, 2016; 11(5):e0155660.
59. Weng TY, Wang CY, Hung YH, Chen WC, Chen YL, Lai MD. Differential Expression Pattern of THBS1 and THBS2 in Lung Cancer: Clinical Outcome and a Systematic-Analysis of Microarray Databases. PLoS One, 2016; 11(8):e0161007.
60. Rhodes DR, Yu J, Shanker K, Deshpande N, Varambally R, Ghosh D, Barrette T, Pandey A, Chinnaiyan AM. ONCOMINE: a cancer microarray database and integrated data-mining platform. Neoplasia, 2004; 6(1):1-6.
61. Györffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, Szallasi Z. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat., 2010; 123(3):725-31.
62. Curtis C., et al. The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature, 2012; 486(7403):346-52.
63. Uhlén M, Fagerberg L. et al. Proteomics. Tissue-based map of the human proteome. Science, 2015; 347(6220):1260419.
64. Fierro AC, Vandenbussche F, Engelen K, Van de Peer Y, Marchal K. Meta Analysis of Gene Expression Data within and Across Species. Curr Genomics. 2008; 9(8):525-34.
65. Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012; 490(7418):61-70.
66. Ciriello G. et al. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer. Cell, 2015; 163(2):506-19.
67. Pereira B. et al. The somatic mutation profiles of 2,433 breast cancers refines their genomic and transcriptomic landscapes. Nat Commun., 2016; 7:11479.
68. Bessarabova M, Ishkin A, JeBailey L, Nikolskaya T, Nikolsky Y. Knowledge-based analysis of proteomics data. BMC Bioinformatics, 2012; 13 Suppl 16:S13.
69. Barretina J. et al. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature. 2012; 483(7391):603-7.
70. Webb DJ, Donais K, Whitmore LA, Thomas SM, Turner CE, Parsons JT, Horwitz AF. FAK-Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol., 2004; 6(2):154-61.
71. Symmans WF. et al. Genomic index of sensitivity to endocrine therapy for breast cancer. J Clin Oncol. 2010; 28(27):4111-9.
72. Desmedt C, Yates L, Kulka J. Catalog of genetic progression of human cancers: breast cancer. Cancer Metastasis Rev., 2016; 35(1):49-62.
73. Song E and Mechref Y. Defining glycoprotein cancer biomarkers by MS in conjunction with glycoprotein enrichment. Biomark Med. 2015; 9(9):835-44.
74. Mechref Y, Hu Y, Garcia A, Hussein A. Identifying cancer biomarkers by mass spectrometry-based glycomics. Electrophoresis. 2012; 33(12):1755–1767.
75. Hart GW and Copeland RJ. Glycomics hits the big time. Cell. 2010; 143(5):672–676.
76. Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer. 2009; 9(12):874-85.
77. Singh AP, Senapati S, Ponnusamy MP, Jain M, Lele SM, Davis JS, Remmenga S, Batra SK. Clinical potential of mucins in diagnosis, prognosis, and therapy of ovarian cancer. Lancet Oncol. 2008; 9(11):1076-85.
78. Wang D, Lu P, Zhang H, Luo M, Zhang X, Wei X, Gao J, Zhao Z, Liu C. Oct-4 and Nanog promote the epithelial-mesenchymal transition of breast cancer stem cells and are associated with poor prognosis in breast cancer patients. Oncotarget, 2014; 5(21):10803-15.
79. von Mering C, Jensen LJ, Snel B, Hooper SD, Krupp M, Foglierini M, Jouffre N, Huynen MA, Bork P. STRING: known and predicted protein-protein associations, integrated and transferred across organisms. Nucleic Acids Res., 2005; 33(Database issue):D433-7.
80. Hsu HP,Lai MD, Lee JC, Yen MC, Weng TY, Chen WC, Fang JH, Chen YL. Mucin 2 silencing promotes colon cancer metastasis through interleukin-6 signaling. Sci Rep., 2017; 7(1):5823.
81. Dey P. et al. Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer. Nature, 2017; 542: 119–123.
82. Snyder KA. et al. Podocalyxin enhances breast tumor growth and metastasis and is a target for monoclonal antibody therapy. Breast Cancer Res., 2015; 17(1): 46.
83. Liu P. et al. Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature. 2014; 508(7497):541-5.
84. Munugalavadla V, Dore LC, Tan BL, Hong L, Vishnu M, Weiss MJ, Kapur R. Repression of c-kit and its downstream substrates by GATA-1 inhibits cell proliferation during erythroid maturation. Mol Cell Biol., 2005; 25(15):6747-59.
85. Zhang Y, Chen Y, Chen D, Jiang Y, Huang W, Ouyang H, Xing W, Zeng M, Xie X, Zeng W. Impact of preoperative anemia on relapse and survival in breast cancer patients. BMC Cancer, 2014; 14:844.
86. Zhang J, Zhu Z, Wu H, Yu Z, Rong Z, Luo Z, Xu Y, Huang K, Qiu Z, Huang C. PODXL, negatively regulated by KLF4, promotes the EMT and metastasis and serves as a novel prognostic indicator of gastric cancer. Gastric Cancer, 2018.
87. Meng X, Ezzati P, Wilkins JA. Requirement of podocalyxin in TGF-beta induced epithelial mesenchymal transition. PLoS One, 2011; 6(4):e18715.
88. Bill R and Christofori G. The relevance of EMT in breast cancer metastasis: Correlation or causality? FEBS Lett., 2015; 589(14):1577-87.
89. Nielsen JS and McNagny KM. CD34 is a key regulator of hematopoietic stem cell trafficking to bone marrow and mast cell progenitor trafficking in the periphery. Microcirculation, 2009; 16(6):487-96.
90. Martin TA and Jiang WG. Evaluation of the expression of stem cell markers in human breast cancer reveals a correlation with clinical progression and metastatic disease in ductal carcinoma. Oncol Rep., 2014; 31(1):262-72.
91. Mine T, Matsueda S, Li Y, Tokumitsu H, Gao H, Danes C, Wong KK, Wang X, Ferrone S, Ioannides CG. Breast cancer cells expressing stem cell markers CD44+ CD24 lo are eliminated by Numb-1 peptide-activated T cells. Cancer Immunol Immunother., 2009; 58(8):1185-94.
92. Kapucuoğlu N, Bozkurt KK, Başpınar Ş, Koçer M, Eroğlu HE, Akdeniz R, Akçil M. The clinicopathological and prognostic significance of CD24, CD44, CD133, ALDH1 expressions in invasive ductal carcinoma of the breast: CD44/CD24 expression in breast cancer. Pathol Res Pract, 2015; 211(10):740-7.
93. Laranjo M, Carvalho MJ, Costa T, Alves A, Oliveira RC, Casalta-Lopes J, Cordeiro P, Botas F, Abrantes AM, Paiva A, Oliveira C, Botelho MF. Mammospheres of hormonal receptor positive breast cancer diverge to triple-negative phenotype. Breast, 2018; 38:22-29.
94. Wilson C, Nicholes K, Bustos D, Lin E, Song Q, Stephan JP, Kirkpatrick DS, Settleman J. Overcoming EMT-associated resistance to anti-cancer drugs via Src/FAK pathway inhibition. Oncotarget, 2014; 5(17):7328-41.
95. Mitra A, Mitra A, Mishra L, Li S. EMT, CTCs and CSCs in tumor relapse and drug-resistance. Oncotarget, 2015; 6(13):10697-711.
96. Yang X, Du G, Yu Z, Si Y, Martin TA, He J, Cheng S, Jiang WG. A Novel NHERF1 Mutation in Human Breast Cancer and Effects on Malignant Progression. Anticancer Res., 2017; 37(1):67-73.
97. Mangia A, Chiriatti A, Bellizzi A, Malfettone A, Stea B, Zito FA, Reshkin SJ, Simone G, Paradiso A. Biological role of NHERF1 protein expression in breast cancer. Histopathology, 2009; 55(5):600-8.
98. Vaquero J, Nguyen Ho-Bouldoires TH, Clapéron A, Fouassier L. Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: from signaling regulation to clinical relevance. Oncogene, 2017; 36(22):3067-3079.
99. Jeong J, VanHouten JN, Kim W, Dann P, Sullivan C, Choi J, Sneddon WB, Friedman PA, Wysolmerski JJ. The scaffolding protein NHERF1 regulates the stability and activity of the tyrosine kinase HER2. J Biol Chem., 2017; 292(16):6555-6568.
100. Lazar CS, Cresson CM, Lauffenburger DA, Gill GN. The Na+/H+ exchanger regulatory factor stabilizes epidermal growth factor receptors at the cell surface. Mol Biol Cell., 2004; 15(12):5470-80.
101. Schmieder S, Nagai M, Orlando RA, Takeda T, Farquhar MG. Podocalyxin activates RhoA and induces actin reorganization through NHERF1 and Ezrin in MDCK cells. J Am Soc Nephrol. 2004; 15(9):2289-98.
102. Zins K, Lucas T, Reichl P, Abraham D, Aharinejad S. A Rac1/Cdc42 GTPase-specific small molecule inhibitor suppresses growth of primary human prostate cancer xenografts and prolongs survival in mice. PLoS One, 2013; 8(9):e74924.
103. Murga C, Zohar M, Teramoto H, Gutkind JS. Rac1 and RhoG promote cell survival by the activation of PI3K and Akt, independently of their ability to stimulate JNK and NF-kappaB. Oncogene. 2002; 21(2):207-16.
104. Zhu G, Fan Z, Ding M, Zhang H, Mu L, Ding Y, Zhang Y, Jia B, Chen L, Chang Z, Wu W. An EGFR/PI3K/AKT axis promotes accumulation of the Rac1-GEF Tiam1 that is critical in EGFR-driven tumorigenesis. Oncogene. 2015; 34(49):5971-82.
105. Song GJ. et al. Phosphorylation of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) by Akt promotes stability and mitogenic function of S-phase kinase-associated protein-2 (Skp2). J Biol Chem., 2015; 290(5):2879-87.
106. Lee JS, Leem SH, Lee SY, Kim SC, Park ES, Kim SB, Kim SK, Kim YJ, Kim WJ, Chu IS. Expression signature of E2F1 and its associated genes predict superficial to invasive progression of bladder tumors. J Clin Oncol., 2010; 28(16):2660-7.
107. Scotto L, Narayan G, Nandula SV, Arias-Pulido H, Subramaniyam S, Schneider A, Kaufmann AM, Wright JD, Pothuri B, Mansukhani M, Murty VV. Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression. Genes Chromosomes Cancer, 2008; 47(9):755-65.
108. Kim SM, Park YY, Park ES, Cho JY, Izzo JG, Zhang D, Kim SB, Lee JH, Bhutani MS, Swisher SG, Wu X, Coombes KR, Maru D, Wang KK, Buttar NS, Ajani JA, Lee JS. Prognostic biomarkers for esophageal adenocarcinoma identified by analysis of tumor transcriptome. PLoS One, 2010; 5(11):e15074.
109. Su LJ, Chang CW, Wu YC, Chen KC, Lin CJ, Liang SC, Lin CH, Whang-Peng J, Hsu SL, Chen CH, Huang CY. Selection of DDX5 as a novel internal control for Q-RT-PCR from microarray data using a block bootstrap re-sampling scheme. BMC Genomics, 2007; 8:140.
110. Selamat SA, Chung BS, Girard L, Zhang W, Zhang Y, Campan M, Siegmund KD, Koss MN, Hagen JA, Lam WL, Lam S, Gazdar AF, Laird-Offringa IA. Genome-scale analysis of DNA methylation in lung adenocarcinoma and integration with mRNA expression. Genome Res., 2012; 22(7):1197-211.
111. Hou J, Aerts J, den Hamer B, van Ijcken W, den Bakker M, Riegman P, van der Leest C, van der Spek P, Foekens JA, Hoogsteden HC, Grosveld F, Philipsen S. Gene expression-based classification of non-small cell lung carcinomas and survival prediction. PLoS One, 2010; 5(4):e10312.
112. Talantov D, Mazumder A, Yu JX, Briggs T, Jiang Y, Backus J, Atkins D, Wang Y. Novel genes associated with malignant melanoma but not benign melanocytic lesions. Clin Cancer Res., 2005; 11(20):7234-42.
113. Vanaja DK, Cheville JC, Iturria SJ, Young CY. Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression. Cancer Res., 2003; 63(14):3877-82.
114. van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R, Friend SH. Gene expression profiling predicts clinical outcome of breast cancer. Nature, 2002; 415(6871):530-6.