The Journal of Membrane Biology

, Volume 242, Issue 2, pp 69–74

Membrane Proteins: The Key Players of a Cancer Cell

Topical Review


Membrane proteins are involved in the prognosis of the most common forms of cancer. Membrane proteins are the hallmark of a cancer cell. The overexpressed membrane receptors are becoming increasingly important in cancer cell therapy. Current renewing therapy approaches based on receptor overexpression include; antibody therapy, nanocarrier drug delivery, and fluorescent tumor imaging in surgery. Gene profiling reveals cancer specific signatures and may identify membrane proteins that are related to cancer progression and lead to the development of improved therapy strategies in the future.


Cancer therapy Gene expression profiling Membrane proteins Nanocarriers Receptor tyrosine kinases Surgery 


  1. Assouline S, Lipton JH (2011) Monitoring response and resistance to treatment in chronic myeloid leukemia. Curr Oncol 18:e71–e83PubMedCrossRefGoogle Scholar
  2. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, Raben D, Baselga J, Spencer SA, Zhu J, Youssoufian H, Rowinsky EK, Ang KK (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11:21–28PubMedCrossRefGoogle Scholar
  3. Chiun-Wei H, Zibo L, Hancheng C, Tony S, Peter SC (2011) Novel alpha(2)beta(1) integrin-targeted peptide probes for prostate cancer imaging. Mol Imaging 10:284–294Google Scholar
  4. Cook N, Basu B, Biswas S, Kareclas P, Mann C, Palmer C, Thomas A, Nicholson S, Morgan B, Lomas D, Sirohi B, Mander AP, Middleton M, Corrie PG (2010) A phase 2 study of vatalanib in metastatic melanoma patients. Eur J Cancer 46:2671–2673PubMedCrossRefGoogle Scholar
  5. Crane LM, van Oosten M, Pleijhuis RG, Motekallemi A, Dowdy SC, Cliby WA, van der Zee AG, van Dam GM (2011) Intraoperative imaging in ovarian cancer: fact or fiction? Mol Imaging 10:248–257PubMedGoogle Scholar
  6. Czuczman MS, Gregory SA (2010) The future of CD20 monoclonal antibody therapy in B-cell malignancies. Leuk Lymphoma 51:983–994PubMedCrossRefGoogle Scholar
  7. Das PM, Thor AD, Edgerton SM, Barry SK, Chen DF, Jones FE (2010) Reactivation of epigenetically silenced HER4/ERBB4 results in apoptosis of breast tumor cells. Oncogene 29:5214–5219PubMedCrossRefGoogle Scholar
  8. Fukuda R, Kelly B, Semenza GL (2003) Vascular endothelial growth factor gene expression in colon cancer cells exposed to prostaglandin E2 is mediated by hypoxia-inducible factor 1. Cancer Res 63:2330–2334PubMedGoogle Scholar
  9. Gan Y, Shi C, Inge L, Hibner M, Balducci J, Huang Y (2010) Differential roles of ERK and Akt pathways in regulation of EGFR-mediated signaling and motility in prostate cancer cells. Oncogene 29:4947–4958PubMedCrossRefGoogle Scholar
  10. Gentles AJ, Plevritis SK, Majeti R, Alizadeh AA (2010) Association of a leukemic stem cell gene expression signature with clinical outcomes in acute myeloid leukemia. JAMA 304:2706–2715PubMedCrossRefGoogle Scholar
  11. Kantelhardt SR, Caarls W, de Vries AH, Hagen GM, Jovin TM, Schulz-Schaeffer W, Rohde V, Giese A, Arndt-Jovin DJ (2010) Specific visualization of glioma cells in living low-grade tumor tissue. PLoS One 5:e11323PubMedCrossRefGoogle Scholar
  12. Koretz K, Bruderlein S, Henne C, Moller P (1993) Expression of CD59, a complement regulator protein and a second ligand of the CD2 molecule, and CD46 in normal and neoplastic colorectal epithelium. Br J Cancer 68:926–931PubMedCrossRefGoogle Scholar
  13. Langenberg MH, Witteveen PO, Lankheet NA, Roodhart JM, Rosing H, van den Heuvel IJ, Beijnen JH, Voest EE (2010) Phase 1 study of combination treatment with PTK 787/ZK 222584 and cetuximab for patients with advanced solid tumors: safety, pharmacokinetics, pharmacodynamics analysis. Neoplasia 12:206–213PubMedGoogle Scholar
  14. Lee H, Akers W, Bhushan K, Bloch S, Sudlow G, Tang R, Achilefu S (2011) Near-infrared pH-activatable fluorescent probes for imaging primary and metastatic breast tumors. Bioconjug Chem 22:777–784PubMedCrossRefGoogle Scholar
  15. Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF (2007) The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med 356:217–226PubMedCrossRefGoogle Scholar
  16. Mackey J, Gelmon K, Martin M, McCarthy N, Pinter T, Rupin M, Youssoufian H (2009) TRIO-012: a multicenter, multinational, randomized, double-blind phase III study of IMC-1121B plus docetaxel versus placebo plus docetaxel in previously untreated patients with HER2-negative, unresectable, locally recurrent or metastatic breast cancer. Clin Breast Cancer 9:258–261PubMedCrossRefGoogle Scholar
  17. Madjd Z, Pinder SE, Paish C, Ellis IO, Carmichael J, Durrant LG (2003) Loss of CD59 expression in breast tumours correlates with poor survival. J Pathol 200:633–639PubMedCrossRefGoogle Scholar
  18. Maeng JH, Lee DH, Jung KH, Bae YH, Park IS, Jeong S, Jeon YS, Shim CK, Kim W, Kim J, Lee J, Lee YM, Kim JH, Kim WH, Hong SS (2010) Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer. Biomaterials 31:4995–5006PubMedCrossRefGoogle Scholar
  19. McNeeley KM, Karathanasis E, Annapragada AV, Bellamkonda RV (2009) Masking and triggered unmasking of targeting ligands on nanocarriers to improve drug delivery to brain tumors. Biomaterials 30:3986–3995PubMedCrossRefGoogle Scholar
  20. Metro G, Finocchiaro G, Toschi L, Bartolini S, Magrini E, Cancellieri A, Trisolini R, Castaldini L, Tallini G, Crino L, Cappuzzo F (2006) Epidermal growth factor receptor (EGFR) targeted therapies in non-small cell lung cancer (NSCLC). Rev Recent Clin Trials 1:1–13PubMedCrossRefGoogle Scholar
  21. Milane L, Duan Z, Amiji M (2011) Development of EGFR-targeted polymer blend nanocarriers for combination paclitaxel/lonidamine delivery to treat multi-drug resistance in human breast and ovarian tumor cells. Mol Pharm 8:185–203PubMedCrossRefGoogle Scholar
  22. Noguchi M, Mizukami Y, Kinoshita K, Earashi M, Thomas M, Miyazaki I (1994) The prognostic significance of epidermal growth factor receptor expression in breast cancer. Surg Today 24:889–894PubMedCrossRefGoogle Scholar
  23. Okines AF, Dewdney A, Chau I, Rao S, Cunningham D (2010) Trastuzumab for gastric cancer treatment. Lancet 376:1736–1737PubMedCrossRefGoogle Scholar
  24. Oyama T, Miyoshi Y, Koyama K, Nakagawa H, Yamori T, Ito T, Matsuda H, Arakawa H, Nakamura Y (2000) Isolation of a novel gene on 8p21.3-22 whose expression is reduced significantly in human colorectal cancers with liver metastasis. Genes Chromosomes Cancer 29:9–15PubMedCrossRefGoogle Scholar
  25. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2:751–760PubMedCrossRefGoogle Scholar
  26. Poptani H (2010) EGFR targeted fluorescence imaging in gliomas. Acad Radiol 17:1–2PubMedCrossRefGoogle Scholar
  27. Roboz GJ, Giles FJ, List AF, Cortes JE, Carlin R, Kowalski M, Bilic S, Masson E, Rosamilia M, Schuster MW, Laurent D, Feldman EJ (2006) Phase 1 study of PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor, for the treatment of acute myeloid leukemia and myelodysplastic syndrome. Leukemia 20:952–957PubMedCrossRefGoogle Scholar
  28. Sah JF, Balasubramanian S, Eckert RL, Rorke EA (2004) Epigallocatechin-3-gallate inhibits epidermal growth factor receptor signaling pathway. Evidence for direct inhibition of ERK1/2 and AKT kinases. J Biol Chem 279:12755–12762PubMedCrossRefGoogle Scholar
  29. Sampath L, Kwon S, Ke S, Wang W, Schiff R, Mawad ME, Sevick-Muraca EM (2007) Dual-labeled trastuzumab-based imaging agent for the detection of human epidermal growth factor receptor 2 overexpression in breast cancer. J Nucl Med 48:1501–1510PubMedCrossRefGoogle Scholar
  30. Schlomm T, Kirstein P, Iwers L, Daniel B, Steuber T, Walz J, Chun FH, Haese A, Kollermann J, Graefen M, Huland H, Sauter G, Simon R, Erbersdobler A (2007) Clinical significance of epidermal growth factor receptor protein overexpression and gene copy number gains in prostate cancer. Clin Cancer Res 13:6579–6584PubMedCrossRefGoogle Scholar
  31. Serra V, Scaltriti M, Prudkin L, Eichhorn PJ, Ibrahim YH, Chandarlapaty S, Markman B, Rodriguez O, Guzman M, Rodriguez S, Gili M, Russillo M, Parra JL, Singh S, Arribas J, Rosen N, Baselga J (2011) PI3K inhibition results in enhanced HER signaling and acquired ERK dependency in HER2-overexpressing breast cancer. Oncogene 30:2547–2557PubMedCrossRefGoogle Scholar
  32. Shimizu M, Shirakami Y, Sakai H, Yasuda Y, Kubota M, Adachi S, Tsurumi H, Hara Y, Moriwaki H (2010) (−)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells. Chem Biol Interact 185:247–252PubMedCrossRefGoogle Scholar
  33. Smith-Jones PM, Pandit-Taskar N, Cao W, O’Donoghue J, Philips MD, Carrasquillo J, Konner JA, Old LJ, Larson SM (2008) Preclinical radioimmunotargeting of folate receptor alpha using the monoclonal antibody conjugate DOTA-MORAb-003. Nucl Med Biol 35:343–351PubMedCrossRefGoogle Scholar
  34. Sosman JA, Puzanov I, Atkins MB (2007) Opportunities and obstacles to combination targeted therapy in renal cell cancer. Clin Cancer Res 13:764s–769sPubMedCrossRefGoogle Scholar
  35. Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S, Leong S, O’Bryant C, Chow LQ, Serkova NJ, Meropol NJ, Lewis NL, Chiorean EG, Fox F, Youssoufian H, Rowinsky EK, Eckhardt SG (2010) Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 28:780–787PubMedCrossRefGoogle Scholar
  36. Steelman LS, Chappell WH, Abrams SL, Kempf RC, Long J, Laidler P, Mijatovic S, Maksimovic-Ivanic D, Stivala F, Mazzarino MC, Donia M, Fagone P, Malaponte G, Nicoletti F, Libra M, Milella M, Tafuri A, Bonati A, Bäsecke J, Cocco L, Evangelisti C, Martelli AM, Montalto G, Cervello M, McCubrey JA (2011) Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging. Aging (Albany NY) 3:192–222Google Scholar
  37. Themelis G, Harlaar NJ, Kelder W et al (2011) Enhancing surgical vision by using real-time imaging of alpha(v)beta (3)-integrin targeted near-infrared fluorescent agent. Ann Surg Oncol. doi:10.1245/s10434-011-1664-9
  38. Toikkanen S, Helin H, Isola J, Joensuu H (1992) Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up. J Clin Oncol 10:1044–1048PubMedGoogle Scholar
  39. Viani GA, Afonso SL, Stefano EJ, De Fendi LI, Soares FV (2007) Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials. BMC Cancer 7:153PubMedCrossRefGoogle Scholar
  40. Woyach JA, Ruppert AS, Heerema NA, Peterson BL, Gribben JG, Morrison VA, Rai KR, Larson RA, Byrd JC (2011) Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: long-term follow-up of CALGB study 9712. J Clin Oncol 29:1349–1355PubMedCrossRefGoogle Scholar
  41. Xu C, Jung M, Burkhardt M, Stephan C, Schnorr D, Loening S, Jung K, Dietel M, Kristiansen G (2005) Increased CD59 protein expression predicts a PSA relapse in patients after radical prostatectomy. Prostate 62:224–232PubMedCrossRefGoogle Scholar
  42. Yau T, Chan P, Pang R, Ng K, Fan ST, Poon RT (2010) Phase 1–2 trial of PTK787/ZK222584 combined with intravenous doxorubicin for treatment of patients with advanced hepatocellular carcinoma: implication for antiangiogenic approach to hepatocellular carcinoma. Cancer 116:5022–5029PubMedCrossRefGoogle Scholar
  43. You B, Chen EX (2011) Anti-EGFR monoclonal antibodies for treatment of colorectal cancers: development of cetuximab and panitumumab. J Clin Pharmacol. doi:10.1177/0091270010395940
  44. Zhang Y, Wang L, Zhang M, Jin M, Wang X (2011) Potential mechanism of interleukin-8 production from lung cancer cells: an involvement of EGF-EGFR-PI3K-Atk-Erk pathway. J Cell Physiol. doi:10.1002/jcp.22722

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children’s Hospital, University Medical Center GroningenUniversity of GroningenGroningenThe Netherlands

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