Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Cancer cell-intrinsic function of CD177 in attenuating β-catenin signaling

Oncogene volume 39, pages 2877–2889 (2020)Cite this article

Subjects

Abstract

Aiming to identify immune molecules with a novel function in cancer pathogenesis, we found the cluster of differentiation 177 (CD177), a known neutrophil antigen, to be positively correlated with relapse-free, metastasis-free, or overall survival in breast cancer. In addition, CD177 expression is correlated with good prognosis in several other solid cancers including prostate, cervical, and lung. Focusing on breast cancer, we found that CD177 is expressed in normal breast epithelial cells and is significantly reduced in invasive cancers. Loss of CD177 leads to hyperproliferative mammary epithelium and contributes to breast cancer pathogenesis. Mechanistically, we found that CD177-deficiency is associated with an increase in β-catenin signaling. Here we identified CD177 as a novel regulator of mammary epithelial proliferation and breast cancer pathogenesis likely via the modulation of Wnt/β-catenin signaling pathway, a key signaling pathway involved in multiple cancer types.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: CD177 is commonly lost in invasive cancer and positively correlated with survival.
Fig. 2: CD177 deficiency leads to proliferative mammary epithelial cells.
Fig. 3: CD177 suppresses breast cancer cell growth and colony formation.
Fig. 4: CD177 suppresses tumorigenesis in a cancer cell-intrinsic manner.
Fig. 5: CD177 attenuates the canonical Wnt/β-catenin signaling.
Fig. 6: CD177 indirectly interacts with β-catenin.

Similar content being viewed by others

References

  1. Temerinac S, Klippel S, Strunck E, Roder S, Lubbert M, Lange W, et al. Cloning of PRV-1, a novel member of the uPAR receptor superfamily, which is overexpressed in polycythemia rubra vera. Blood. 2000;95:2569–76.

    Article  CAS  PubMed  Google Scholar 

  2. Kissel K, Santoso S, Hofmann C, Stroncek D, Bux J. Molecular basis of the neutrophil glycoprotein NB1 (CD177) involved in the pathogenesis of immune neutropenias and transfusion reactions. Eur J Immunol. 2001;31:1301–9.

    Article  CAS  PubMed  Google Scholar 

  3. Caruccio L, Bettinotti M, Director-Myska AE, Arthur DC, Stroncek D. The gene overexpressed in polycythemia rubra vera, PRV-1, and the gene encoding a neutrophil alloantigen, NB1, are alleles of a single gene, CD177, in chromosome band 19q13.31. Transfusion. 2006;46:441–7.

    Article  CAS  PubMed  Google Scholar 

  4. Passamonti F, Pietra D, Malabarba L, Rumi E, Della Porta MG, Malcovati L, et al. Clinical significance of neutrophil CD177 mRNA expression in Ph-negative chronic myeloproliferative disorders. Br J Haematol. 2004;126:650–6.

    Article  CAS  PubMed  Google Scholar 

  5. Xie Q, Klesney-Tait J, Keck K, Parlet C, Borcherding N, Kolb R, et al. Characterization of a novel mouse model with genetic deletion of CD177. Protein Cell. 2015;6:117–26.

    Article  CAS  PubMed  Google Scholar 

  6. Dalerba P, Kalisky T, Sahoo D, Rajendran PS, Rothenberg ME, Leyrat AA, et al. Single-cell dissection of transcriptional heterogeneity in human colon tumors. Nat Biotechnol. 2011;29:1120–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Toyoda T, Tsukamoto T, Yamamoto M, Ban H, Saito N, Takasu S, et al. Gene expression analysis of a Helicobacter pylori-infected and high-salt diet-treated mouse gastric tumor model: identification of CD177 as a novel prognostic factor in patients with gastric cancer. BMC Gastroenterol. 2013;13:122.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17:9–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Clevers H, Nusse R. Wnt/beta-catenin signaling and disease. Cell. 2012;149:1192–205.

    Article  CAS  PubMed  Google Scholar 

  10. Eger A, Stockinger A, Schaffhauser B, Beug H, Foisner R. Epithelial mesenchymal transition by c-Fos estrogen receptor activation involves nuclear translocation of beta-catenin and upregulation of beta-catenin/lymphoid enhancer binding factor-1 transcriptional activity. J Cell Biol. 2000;148:173–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Orsulic S, Huber O, Aberle H, Arnold S, Kemler R. E-cadherin binding prevents beta-catenin nuclear localization and beta-catenin/LEF-1-mediated transactivation. J Cell Sci. 1999;112:1237–45.

    CAS  PubMed  Google Scholar 

  12. Kuphal F, Behrens J. E-cadherin modulates Wnt-dependent transcription in colorectal cancer cells but does not alter Wnt-independent gene expression in fibroblasts. Exp Cell Res. 2006;312:457–67.

    Article  CAS  PubMed  Google Scholar 

  13. Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008;68:3645–54.

    Article  CAS  PubMed  Google Scholar 

  14. Stockinger A, Eger A, Wolf J, Beug H, Foisner R. E-cadherin regulates cell growth by modulating proliferation-dependent beta-catenin transcriptional activity. J Cell Biol. 2001;154:1185–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sanson B, White P, Vincent JP. Uncoupling cadherin-based adhesion from wingless signalling in Drosophila. Nature. 1996;383:627–30.

    Article  PubMed  Google Scholar 

  16. Heasman J, Ginsberg D, Geiger B, Goldstone K, Pratt T, Yoshida-Noro C, et al. A functional test for maternally inherited cadherin in Xenopus shows its importance in cell adhesion at the blastula stage. Development. 1994;120:49–57.

    CAS  PubMed  Google Scholar 

  17. Gottardi CJ, Wong E, Gumbiner BM. E-cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesion-independent manner. J Cell Biol. 2001;153:1049–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fagotto F, Funayama N, Gluck U, Gumbiner BM. Binding to cadherins antagonizes the signaling activity of beta-catenin during axis formation in Xenopus. J Cell Biol. 1996;132:1105–14.

    Article  CAS  PubMed  Google Scholar 

  19. Incassati A, Chandramouli A, Eelkema R, Cowin P. Key signaling nodes in mammary gland development and cancer: beta-catenin. Breast Cancer Res. 2010;12:213.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Polakis P. The many ways of Wnt in cancer. Curr Opin Genet Dev. 2007;17:45–51.

    Article  CAS  PubMed  Google Scholar 

  21. Koesters R, Ridder R, Kopp-Schneider A, Betts D, Adams V, Niggli F, et al. Mutational activation of the beta-catenin proto-oncogene is a common event in the development of Wilms’ tumors. Cancer Res. 1999;59:3880–2.

    CAS  PubMed  Google Scholar 

  22. Chiurillo MA. Role of the Wnt/beta-catenin pathway in gastric cancer: an in-depth literature review. World J Exp Med. 2015;5:84–102.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Badders NM, Goel S, Clark RJ, Klos KS, Kim S, Bafico A, et al. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage. PLoS ONE. 2009;4:e6594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lindvall C, Evans NC, Zylstra CR, Li Y, Alexander CM, Williams BO. The Wnt signaling receptor Lrp5 is required for mammary ductal stem cell activity and Wnt1-induced tumorigenesis. J Biol Chem. 2006;281:35081–7.

    Article  CAS  PubMed  Google Scholar 

  25. Lindvall C, Zylstra CR, Evans N, West RA, Dykema K, Furge KA, et al. The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development. PLoS ONE. 2009;4:e5813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Tepera SB, McCrea PD, Rosen JM. A beta-catenin survival signal is required for normal lobular development in the mammary gland. J Cell Sci. 2003;116:1137–49.

    Article  CAS  PubMed  Google Scholar 

  27. Brisken C, Heineman A, Chavarria T, Elenbaas B, Tan J, Dey SK, et al. Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev. 2000;14:650–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Chu EY, Hens J, Andl T, Kairo A, Yamaguchi TP, Brisken C, et al. Canonical Wnt signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development. 2004;131:4819–29.

    Article  CAS  PubMed  Google Scholar 

  29. Zeng YA, Nusse R. Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture. Cell Stem Cell. 2010;6:568–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Teuliere J, Faraldo MM, Deugnier MA, Shtutman M, Ben-Ze’ev A, Thiery JP, et al. Targeted activation of beta-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia. Development. 2005;132:267–77.

    Article  CAS  PubMed  Google Scholar 

  31. Zhang J, Li Y, Liu Q, Lu W, Bu G. Wnt signaling activation and mammary gland hyperplasia in MMTV-LRP6 transgenic mice: implication for breast cancer tumorigenesis. Oncogene. 2010;29:539–49.

    Article  CAS  PubMed  Google Scholar 

  32. Imbert A, Eelkema R, Jordan S, Feiner H, Cowin P. Delta N89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland. J Cell Biol. 2001;153:555–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tsukamoto AS, Grosschedl R, Guzman RC, Parslow T, Varmus HE. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell. 1988;55:619–25.

    Article  CAS  PubMed  Google Scholar 

  34. Hayes MJ, Thomas D, Emmons A, Giordano TJ, Kleer CG. Genetic changes of Wnt pathway genes are common events in metaplastic carcinomas of the breast. Clin Cancer Res. 2008;14:4038–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ozaki S, Ikeda S, Ishizaki Y, Kurihara T, Tokumoto N, Iseki M, et al. Alterations and correlations of the components in the Wnt signaling pathway and its target genes in breast cancer. Oncol Rep. 2005;14:1437–43.

    CAS  PubMed  Google Scholar 

  36. Prasad CP, Gupta SD, Rath G, Ralhan R. Wnt signaling pathway in invasive ductal carcinoma of the breast: relationship between beta-catenin, dishevelled and cyclin D1 expression. Oncology. 2007;73:112–7.

    Article  CAS  PubMed  Google Scholar 

  37. Khramtsov AI, Khramtsova GF, Tretiakova M, Huo D, Olopade OI, Goss KH. Wnt/beta-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome. Am J Pathol. 2010;176:2911–20.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Gyorffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, et al. 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;123:725–31.

    Article  CAS  PubMed  Google Scholar 

  39. Wang Y, Klijn JG, Zhang Y, Sieuwerts AM, Look MP, Yang F, et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet. 2005;365:671–9.

    Article  CAS  PubMed  Google Scholar 

  40. Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, et al. Genes that mediate breast cancer metastasis to lung. Nature. 2005;436:518–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4.

    Article  PubMed  Google Scholar 

  43. Feng Q, Zhang Z, Shea MJ, Creighton CJ, Coarfa C, Hilsenbeck SG, et al. An epigenomic approach to therapy for tamoxifen-resistant breast cancer. Cell Res. 2014;24:809–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Matsuzawa A, Tseng PH, Vallabhapurapu S, Luo JL, Zhang W, Wang H, et al. Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science. 2008;321:663–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Veeman MT, Slusarski DC, Kaykas A, Louie SH, Moon RT. Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements. Curr Biol. 2003;13:680–5.

    Article  CAS  PubMed  Google Scholar 

  46. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelsen TS, et al. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science. 2014;343:84–87.

    Article  CAS  PubMed  Google Scholar 

  47. Sanjana NE, Shalem O, Zhang F. Improved vectors and genome-wide libraries for CRISPR screening. Nat Methods. 2014;11:783–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Goecks J, Nekrutenko A, Taylor J, Galaxy T. Galaxy: a comprehensive approach for supporting accessible, reproducible, and transparent computational research in the life sciences. Genome Biol. 2010;11:R86.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Blankenberg D, Von Kuster G, Coraor N, Ananda G, Lazarus R, Mangan M et al. Galaxy: a web-based genome analysis tool for experimentalists. Curr Protoc Mol Biol 2010; Chapter 19: Unit 19.10.1-21.

  50. Giardine B, Riemer C, Hardison RC, Burhans R, Elnitski L, Shah P, et al. Galaxy: a platform for interactive large-scale genome analysis. Genome Res. 2005;15:1451–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7:562–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Liberzon A, Subramanian A, Pinchback R, Thorvaldsdottir H, Tamayo P, Mesirov JP. Molecular signatures database (MSigDB) 3.0. Bioinformatics. 2011;27:1739–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Uhlen M, Zhang C, Lee S, Sjostedt E, Fagerberg L, Bidkhori G et al. A pathology atlas of the human cancer transcriptome. Science 2017; 357:pii: eaan2507.

  55. Borcherding N, Cole K, Kluz P, Jorgensen M, Kolb R, Bellizzi A, et al. Re-evaluating E-cadherin and beta-catenin: a pan-cancer proteomic approach with an emphasis on breast cancer. Am J Pathol. 2018;188:1910–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Geyer FC, Lacroix-Triki M, Savage K, Arnedos M, Lambros MB, MacKay A, et al. beta-catenin pathway activation in breast cancer is associated with triple-negative phenotype but not with CTNNB1 mutation. Mod Pathol. 2011;24:209–31.

    Article  CAS  PubMed  Google Scholar 

  57. Bulut G, Fallen S, Beauchamp EM, Drebing LE, Sun J, Berry DL, et al. Beta-catenin accelerates human papilloma virus type-16 mediated cervical carcinogenesis in transgenic mice. PLoS ONE. 2011;6:e27243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Chen Q, Cao HZ, Zheng PS. LGR5 promotes the proliferation and tumor formation of cervical cancer cells through the Wnt/beta-catenin signaling pathway. Oncotarget. 2014;5:9092–105.

    PubMed  PubMed Central  Google Scholar 

  59. Zhang YN, Liu BZ, Zhao QY, Hou T, Huang X. Nuclear localizaiton of beta-catenin is associated with poor survival and chemo-/radioresistance in human cervical squamous cell cancer. Int J Clin Exp Pathol. 2014;7:3908–17.

    PubMed  PubMed Central  Google Scholar 

  60. Kypta RM, Waxman J. Wnt/beta-catenin signalling in prostate cancer. Nat Rev Urol. 2012;9:418–28.

    Article  CAS  PubMed  Google Scholar 

  61. Yokoyama NN, Shao S, Hoang BH, Mercola D, Zi X. Wnt signaling in castration-resistant prostate cancer: implications for therapy. Am J Clin Exp Urol. 2014;2:27–44.

    PubMed  PubMed Central  Google Scholar 

  62. Nakashima N, Liu D, Huang CL, Ueno M, Zhang X, Yokomise H. Wnt3 gene expression promotes tumor progression in non-small cell lung cancer. Lung Cancer. 2012;76:228–34.

    Article  PubMed  Google Scholar 

  63. Uematsu K, He B, You L, Xu Z, McCormick F, Jablons DM. Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression. Oncogene. 2003;22:7218–21.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

W.Z. was supported by NIH grants CA200673 and CA203834, the V Scholar award, American Cancer Society seed grant, Breast Cancer Research Award and Oberley Award (National Cancer Institute Award P30CA086862) from Holden Comprehensive Cancer Center at the University of Iowa, University of Iowa. N.B. was supported by NIH CA206255. Q.X. was supported by the National Natural Science Foundation of China (No. 81502313). We thank Dr. Foekens for sharing the site-specific metastasis information related to GSE2034. We thank Dr. Shay for sharing the human colon epithelial cells.

Author information

Author notes

  1. Qing Xie

    Present address: Tumor Signaling and Transduction Laboratory, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453000, China

  2. These authors contributed equally: Paige N. Kluz, Ryan Kolb, Qing Xie

Authors and Affiliations

  1. Department of Pathology, University of Iowa, College of Medicine, Iowa City, IA, 52242-1109, USA

    Paige N. Kluz, Qing Xie, Nicholas Borcherding, Katherine N. Gibson-Corley, Chen Zhao & Andrew Bellizzi

  2. Free Radical and Radiation Biology Program, University of Iowa, College of Medicine, Iowa City, IA, 52242-1109, USA

    Paige N. Kluz, Yuewan Luo, Myung-Chul Kim & Wei Li

  3. Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA

    Ryan Kolb & Weizhou Zhang

  4. Medical Science Training Program, University of Iowa, College of Medicine, Iowa City, IA, 52242-1109, USA

    Nicholas Borcherding

  5. Department of Anatomy and Cell Biology, University of Iowa, College of Medicine, Iowa City, IA, 52242-1109, USA

    Qi Liu & Hank H. Qi

  6. Department of Chemistry, Purdue University, West Lafayette, IN, 47907, USA

    Linna Wang & Andy W. Tao

  7. Department of Biology, College of Life Science, Nankai University, Tianjin, 300071, China

    Yinan Zhang

  8. Department of Biology, University of Iowa, College of Medicine, Iowa City, IA, 52242-1109, USA

    Christopher Stipp

  9. Holden Comprehensive Cancer Center, University of Iowa, College of Medicine, Iowa City, IA, 52242-1109, USA

    Christopher Stipp, Katherine N. Gibson-Corley, Andrew Bellizzi, Sonia Sugg & Ronald J. Weigel

  10. Department of Surgery, University of Iowa, College of Medicine, Iowa City, IA, 52242-1109, USA

    Sonia Sugg & Ronald J. Weigel

  11. Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, FL, 32610, USA

    Daohong Zhou

  12. Division of Gastrointestinal Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Zhejiang, 325035, China

    Xian Shen

Authors
  1. Paige N. Kluz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ryan Kolb
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qing Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nicholas Borcherding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuewan Luo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Myung-Chul Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Linna Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yinan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Wei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Christopher Stipp
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Katherine N. Gibson-Corley
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Chen Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hank H. Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Andrew Bellizzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Andy W. Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Sonia Sugg
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ronald J. Weigel
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Daohong Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Xian Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Weizhou Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

P.N.K., R.K., D.Z., X.S., and W.Z. conceived and designed the experiments. R.K. and Q.X. obtained the mouse tumor data. R.K., P.N.K., Q.X., Q.L.L., M.K., Y.L. did the biochemical studies. P.N.K., Y.L. performed the immunofluorescent staining, immunohistochemistry, and analysis of normal mammary gland. N.B. processed the RNAseq data and obtained methylation data. W.L., C.S., L.W., and A.W.T. provided technical support. A.B. provided TMAs and assigned IHC scores. K.N.G. and C.Z. provided histological help on tumor and tumor mammary tissues., S.S. and R.J.W. provided human breast cancer protein, RNA and tissue samples. R.K., P.N.K., X.S., D.Z., and W.Z. analyzed the data and wrote the manuscript. W.Z. supervised the whole project.

Corresponding authors

Correspondence to Xian Shen or Weizhou Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kluz, P.N., Kolb, R., Xie, Q. et al. Cancer cell-intrinsic function of CD177 in attenuating β-catenin signaling. Oncogene 39, 2877–2889 (2020). https://doi.org/10.1038/s41388-020-1203-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41388-020-1203-x

This article is cited by

Search

Advanced search

Quick links