Cell division cycle associated 7 promoteing breast cancer progression by enhancing proliferation and stemness of breast cancer cell

YANG De-Cao; LIU Cheng; MA Ji; WANG Meng-Yuan; ZHAN Jun; ZHANG Hong-Quan

doi:10.16098/j.issn.0529-1356.2020.06.013

PDF(10017 KB)

Acta Anatomica Sinica ›› 2020, Vol. 51 ›› Issue (6) : 888-896. DOI: 10.16098/j.issn.0529-1356.2020.06.013

Cell division cycle associated 7 promoteing breast cancer progression by enhancing proliferation and stemness of breast cancer cell

YANG De-cao LIU Cheng MA Ji WANG Meng-yuan ZHAN Jun* ZHANG Hong-quan*

Author information +

History +

Abstract

Objective To investigate the role of cell division cycle associated 7 (CDCA7) in breast cancer and the potential mechanisms among the progressioned. Methods By data analysis in data base to retrieve the differential expression gene and find out highly expressed genes in basal-like breast cancer cells. Among these genes we selected the attractive CDCA7 as the target of investigation. Through specimen immunohistochemistry analysis of clinical patients to confirm the significance of the research. Then we constructed CDCA7 stable expression cell lines to preform a series of experiments including colony formation assays, tumorsphere formation assays, flow cytometry, Western blotting and Real-time PCR to clear the role of CDCA7 in breast cancer. Results Data base analysis and histochemistry showed CDCA7 was highly expressed in basal-like breast cancer cells and high expression of CDCA7 predicts poor prognosis. Overexpressing CDCA7 in luminal cell lines, the cell lines showed stronger proliferative capacity, more mitotic cell and less apoptotic cell. Meanwhile, the markers of stem cell, such as CD133 and acetaldehyde dehydrogenase(ALDH) showed being upregulated. The Real-time PCR and Western blotting analysis showed that CDCA7 increased the expression of β-catenin, through which CDCA7 effected the Wnt pathway so as to influence cell proliferation and stemness. Conclusion CDCA7 as a oncogenic gene induces luminal cell to transform to basal-like subtype by depending on β-catenin and Wnt pathway.

Key words

Cell division cycle associated 7 / Basal-like/luminal breast cancer / Stem cell / β-catenin / Flow cytometry / Human

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

YANG De-cao LIU Cheng MA Ji WANG Meng-yuan ZHAN Jun ZHANG Hong-quan. Cell division cycle associated 7 promoteing breast cancer progression by enhancing proliferation and stemness of breast cancer cell[J]. Acta Anatomica Sinica. 2020, 51(6): 888-896 https://doi.org/10.16098/j.issn.0529-1356.2020.06.013

References

［1］ Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012 ［J］. Int J Cancer, 2015, 136(5):E359-386.

［2］ Bianchini G, Balko JM, Mayer IA, et al. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease ［J］. Nat Rev Clin Oncol, 2016, 13(11):674-690.

［3］ Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes ［J］. J Clin Oncol, 2009, 27(8):1160-1167.

［4］ Prat A, Parker JS, Karginova O, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer ［J］. Breast Cancer Res, 2010, 12(5):R68.

［5］ Ricardo S, Vieira AF, Gerhard R, et al. Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype ［J］. J Clin Pathol, 2011, 64(11):937-946.

［6］ Holliday DL, and Speirs V, Choosing the right cell line for breast cancer research ［J］. Breast Cancer Res, 2011, 13(4):215.

［7］ Andersen JN, Sathyanarayanan S, Di Bacco A, et al. Pathway-based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors ［J］. Sci Transl Med, 2010, 2(43):43ra55.

［8］ Dittmer J. Breast cancer stem cells: Features, key drivers and treatment options ［J］. Semin Cancer Biol, 2018, 53:59-74.

［9］ Maugeri-Sacca M, De Maria R. Hippo pathway and breast cancer stem cells ［J］. Crit Rev Oncol Hematol, 2016, 99:115-122.

［10］ Whitfield ML, Sherlock G, Saldanha AJ, et al. Identification of genes periodically expressed in the human cell cycle and their expression in tumors ［J］. Mol Biol Cell, 2002, 13(6):1977-2000.

［11］ Prescott JE, Osthus RC, Lee LA, et al. A novel c-Myc-responsive gene, JPO1, participates in neoplastic transformation ［J］. J Biol Chem, 2001, 276(51):48276-48284.

［12］ Goto Y, Hayashi R, Muramatsu T, et al. JPO1/CDCA7, a novel transcription factor E2F1-induced protein, possesses intrinsic transcriptional regulator activity ［J］. Biochim Biophys Acta, 2006, 1759(12):60-68.

［13］ Guiu J, Bergen DJ, De Pater E, et al. Identification of Cdca7 as a novel Notch transcriptional target involved in hematopoietic stem cell emergence ［J］. J Exp Med, 2014, 211(12):2411-2423.

［14］ Ye L, Li F, Song Y, et al. Overexpression of CDCA7 predicts poor prognosis and induces EZH2-mediated progression of triple-negative breast cancer ［J］. Int J Cancer, 2018, 143(10):2602-2613.

［15］ Nusse R, Clevers H. Wnt/beta-catenin signaling, disease, and emerging therapeutic modalities ［J］. Cell, 2017, 169(6):985-999.

［16］ Van Camp JK, Beckers S, Zegers D, et al. Wnt signaling and the control of human stem cell fate ［J］. Stem Cell Rev Rep, 2014, 10(2):207-229.

［17］ Alexander CM. The wnt signaling landscape of mammary stem cells and breast tumors ［J］. Prog Mol Biol Transl Sci, 2018, 153:271-298.

［18］ Yu QC, Verheyen EM, Zeng YA. Mammary development and breast cancer: a wnt perspective ［J］. Cancers (Basel), 2016, 8(7):65.

［19］ Mohammed MK, Shao C, Wang J, et al. Wnt/beta-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance ［J］. Genes Dis, 2016, 3(1):11-40.

［20］ Domenici G, Aurrekoetxea-Rodriguez I, Simoes BM, et al. A Sox2-Sox9 signalling axis maintains human breast luminal progenitor and breast cancer stem cells ［J］. Oncogene, 2019, 38(17):3151-3169.

［21］ Feng W, Liu S, Zhu R, et al. SOX10 induced Nestin expression regulates cancer stem cell properties of TNBC cells ［J］. Biochem Biophys Res Commun, 2017, 485(2):522-528.

［22］ Ihemelandu CU, Naab TJ, Mezghebe HM, et al. Basal cell-like (triple-negative) breast cancer, a predictor of distant metastasis in African American women ［J］. Am J Surg, 2008, 195(2):153-158.