C1orf106, an innate immunity activator, is amplified in breast cancer and is required for basal-like/luminal progenitor fate decision
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Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes. However, genes that specifically promote basal-like breast cancer development remain largely unknown. Here, we report that a novel gene C1orf106 plays an important role in maintaining the feature of basal-like/luminal progenitors. C1orf106 is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in patients. In human TCGA database, C1orf106 expression was correlated with upregulation of ELF5 and downregulation of GATA3, two transcription factors that regulate mammary gland stem cell fate. Enhanced expression of C1orf106 promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5; depletion of C1orf106 suppresses tumorigenesis and expression of basal-like/luminal progenitor marker GATA3. These findings suggest that C1orf106 maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and GATA3. Taken together, we demonstrated that C1orf106 is an important regulator for basal-like/luminal progenitors and targeting C1orf106 is of therapeutic value for breast cancer.
Key wordsC1orf106 basal-like luminal progenitor breast cancer ELF5 GATA3
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This work was supported by the Ministry of Science and Technology of China (2016YFC1302103 and 2015CB553906), the National Natural Science Foundation of China (81230051, 81472734, 31170711, 81321003, and 30830048), the Beijing Natural Science Foundation (7120002), the 111 Project of the Ministry of Education, Peking University (BMU2018JC004, BMU20120314, and BMU20130364), and a Leading Academic Discipline Project of Beijing Education Bureau to H.Z. This work was also supported by a grant from the National Natural Science Foundation of China (81773199) to J.Z.
Compliance and ethics The author(s) declare that they have no conflict of interest.
- Asselin-Labat, M.L., Sutherland, K.D., Barker, H., Thomas, R., Shackleton, M., Forrest, N.C., Hartley, L., Robb, L., Grosveld, F.G., van der Wees, J., et al. (2007). Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol 9, 201–209.CrossRefGoogle Scholar
- Asselin-Labat, M.L., Sutherland, K.D., Vaillant, F., Gyorki, D.E., Wu, D., Holroyd, S., Breslin, K., Ward, T., Shi, W., Bath, M.L., et al. (2011). Gata-3 negatively regulates the tumor-initiating capacity of mammary luminal progenitor cells and targets the putative tumor suppressor caspase-14. Mol Cell Biol 31, 4609–4622.CrossRefGoogle Scholar
- Chakrabarti, R., Hwang, J., Andres Blanco, M., Wei, Y., Lukačišin, M., Romano, R.A., Smalley, K., Liu, S., Yang, Q., Ibrahim, T., et al. (2012). Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nat Cell Biol 14, 1212–1222.CrossRefGoogle Scholar
- Lim, E., Wu, D., Pal, B., Bouras, T., Asselin-Labat, M.L., Vaillant, F., Yagita, H., Lindeman, G.J., Smyth, G.K., and Visvader, J.E. (2010). transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways. Breast Cancer Res 12, R21.CrossRefGoogle Scholar
- Malorni, L., Shetty, P.B., De Angelis, C., Hilsenbeck, S., Rimawi, M.F., Elledge, R., Osborne, C.K., De Placido, S., and Arpino, G. (2012). Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow-up. Breast Cancer Res Treat 136, 795–804.CrossRefGoogle Scholar
- Molyneux, G., Geyer, F.C., Magnay, F.A., McCarthy, A., Kendrick, H., Natrajan, R., Mackay, A., Grigoriadis, A., Tutt, A., Ashworth, A., et al. (2010). BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell 7, 403–417.CrossRefGoogle Scholar
- Rivas, M.A., Beaudoin, M., Gardet, A., Stevens, C., Sharma, Y., Zhang, C. K., Boucher, G., Ripke, S., Ellinghaus, D., Burtt, N., et al. (2011). Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet 43, 1066–1073.CrossRefGoogle Scholar