Non-canonical functions of the RB protein in cancer (original) (raw)

• Dyson, N. The regulation of E2F by pRB-family proteins. Genes Dev. 12, 2245–2262 (1998).
  Article PubMed CAS Google Scholar
• Classon, M. & Harlow, E. The retinoblastoma tumour suppressor in development and cancer. Nat. Rev. Cancer 2, 910–917 (2002).
  Article PubMed CAS Google Scholar
• Knudsen, E. S. & Knudsen, K. E. Tailoring to RB: tumour suppressor status and therapeutic response. Nat. Rev. Cancer 8, 714–724 (2008).
  Article PubMed PubMed Central CAS Google Scholar
• Sherr, C. J. Cancer cell cycles. Science 274, 1672–1677 (1996).
  Article PubMed CAS Google Scholar
• Sherr, C. J. & McCormick, F. The RB and p53 pathways in cancer. Cancer Cell 2, 103–112 (2002).
  Article PubMed CAS Google Scholar
• Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).
  Article PubMed CAS Google Scholar
• Ishak, C. A. et al. An RB-EZH2 complex mediates silencing of repetitive DNA sequences. Mol. Cell 64, 1074–1087 (2016).
  Article PubMed PubMed Central CAS Google Scholar
• Kareta, M. S. et al. Inhibition of pluripotency networks by the Rb tumor suppressor restricts reprogramming and tumorigenesis. Cell Stem Cell 16, 39–50 (2015).
  Article PubMed CAS Google Scholar
• Ferrari, R. et al. Adenovirus small E1A employs the lysine acetylases p300/CBP and tumor suppressor Rb to repress select host genes and promote productive virus infection. Cell Host Microbe 16, 663–676 (2014).
  Article PubMed PubMed Central CAS Google Scholar
• Avni, D. et al. Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage. Mol. Cell 12, 735–746 (2003).
  Article PubMed CAS Google Scholar
• Wells, J., Yan, P. S., Cechvala, M., Huang, T. & Farnham, P. J. Identification of novel pRb binding sites using CpG microarrays suggests that E2F recruits pRb to specific genomic sites during S phase. Oncogene 22, 1445–1460 (2003).
  Article PubMed CAS Google Scholar
• Ianari, A. et al. Proapoptotic function of the retinoblastoma tumor suppressor protein. Cancer Cell 15, 184–194 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Cecchini, M. J. & Dick, F. A. The biochemical basis of CDK phosphorylation-independent regulation of E2F1 by the retinoblastoma protein. Biochem. J. 434, 297–308 (2011).
  Article PubMed CAS Google Scholar
• Cecchini, M. J. et al. Loss of the retinoblastoma tumor suppressor correlates with improved outcome in patients with lung adenocarcinoma treated with surgery and chemotherapy. Hum. Pathol. 46, 1922–1934 (2015).
  Article PubMed CAS Google Scholar
• Bosco, E. E. et al. The retinoblastoma tumor suppressor modifies the therapeutic response of breast cancer. J. Clin. Invest. 117, 218–228 (2007).
  Article PubMed CAS Google Scholar
• Witkiewicz, A. K. et al. RB-pathway disruption is associated with improved response to neoadjuvant chemotherapy in breast cancer. Clin. Cancer Res. 18, 5110–5122 (2012).
  Article PubMed PubMed Central CAS Google Scholar
• Kommoss, S. et al. Independent prognostic significance of cell cycle regulator proteins p16(INK4a) and pRb in advanced-stage ovarian carcinoma including optimally debulked patients: a translational research subprotocol of a randomised study of the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group. Br. J. Cancer 96, 306–313 (2007).
  Article PubMed PubMed Central CAS Google Scholar
• Ludovini, V. et al. Vascular endothelial growth factor, p53, Rb, Bcl-2 expression and response to chemotherapy in advanced non-small cell lung cancer. Lung Cancer 46, 77–85 (2004).
  Article PubMed Google Scholar
• Zhao, W. et al. Altered p16(INK4) and RB1 expressions are associated with poor prognosis in patients with nonsmall cell lung cancer. J. Oncol. 2012, 957437 (2012).
  Article PubMed PubMed Central CAS Google Scholar
• Garsed, D. W. et al. Homologous recombination DNA repair pathway disruption and retinoblastoma protein loss are associated with exceptional survival in high-grade serous ovarian cancer. Clin. Cancer Res. 24, 569–580 (2017).
  Article PubMed CAS Google Scholar
• Knudsen, E. S. et al. Retinoblastoma and phosphate and tensin homolog tumor suppressors: impact on ductal carcinoma in situ progression. J. Natl Cancer Inst. 104, 1825–1836 (2012).
  Article PubMed PubMed Central CAS Google Scholar
• Sharma, A. et al. The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression. J. Clin. Invest. 120, 4478–4492 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Burkhart, D. L. & Sage, J. Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat. Rev. Cancer 8, 671–682 (2008).
  Article PubMed CAS PubMed Central Google Scholar
• McNair, C. et al. Differential impact of RB status on E2F1 reprogramming in human cancer. J. Clin. Invest. 128, 341–358 (2017).
  Article PubMed PubMed Central Google Scholar
• Robinson, D. R. et al. Integrative clinical genomics of metastatic cancer. Nature 548, 297–303 (2017).
  Article PubMed PubMed Central CAS Google Scholar
• Robinson, D. et al. Integrative clinical genomics of advanced prostate cancer. Cell 162, 454 (2015).
  Article PubMed CAS Google Scholar
• Beltran, H. et al. Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. Nat. Med. 22, 298–305 (2016).
  Article PubMed PubMed Central CAS Google Scholar
• Dick, F. A. & Rubin, S. M. Molecular mechanisms underlying RB protein function. Nat. Rev. Mol. Cell Biol. 14, 297–306 (2013).
  Article PubMed PubMed Central CAS Google Scholar
• Kitajima, S. & Takahashi, C. Intersection of retinoblastoma tumor suppressor function, stem cells, metabolism, and inflammation. Cancer Sci. 108, 1726–1731 (2017).
  Article PubMed PubMed Central CAS Google Scholar
• Nicolay, B. N. & Dyson, N. J. The multiple connections between pRB and cell metabolism. Curr. Opin. Cell Biol. 25, 735–740 (2013).
  Article PubMed CAS Google Scholar
• Benevolenskaya, E. V. & Frolov, M. V. Emerging links between E2F control and mitochondrial function. Cancer Res. 75, 619–623 (2015).
  Article PubMed PubMed Central CAS Google Scholar
• Ciavarra, G. & Zacksenhaus, E. Direct and indirect effects of the pRb tumor suppressor on autophagy. Autophagy 7, 544–546 (2011).
  Article PubMed CAS Google Scholar
• Indovina, P., Pentimalli, F., Casini, N., Vocca, I. & Giordano, A. RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy. Oncotarget 6, 17873–17890 (2015).
  Article PubMed PubMed Central Google Scholar
• Sage, J. The retinoblastoma tumor suppressor and stem cell biology. Genes Dev. 26, 1409–1420 (2012).
  Article PubMed PubMed Central CAS Google Scholar
• Dyson, N. J. RB1: a prototype tumor suppressor and an enigma. Genes Dev. 30, 1492–1502 (2016).
  Article PubMed PubMed Central CAS Google Scholar
• Blanchet, E. et al. E2F transcription factor-1 regulates oxidative metabolism. Nat. Cell Biol. 13, 1146–1152 (2011).
  Article PubMed CAS Google Scholar
• Jones, R. A. et al. RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation. J. Clin. Invest. 126, 3739–3757 (2016).
  Article PubMed PubMed Central Google Scholar
• Lee, W. H. et al. The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity. Nature 329, 642–645 (1987).
  Article PubMed CAS Google Scholar
• Adams, P. D. et al. Retinoblastoma protein contains a C-terminal motif that targets it for phosphorylation by cyclin-cdk complexes. Mol. Cell. Biol. 19, 1068–1080 (1999).
  Article PubMed PubMed Central CAS Google Scholar
• Carr, S. M., Munro, S., Kessler, B., Oppermann, U. & La Thangue, N. B. Interplay between lysine methylation and Cdk phosphorylation in growth control by the retinoblastoma protein. EMBO J. 30, 317–327 (2011).
  Article PubMed CAS Google Scholar
• Munro, S., Khaire, N., Inche, A., Carr, S. & La Thangue, N. B. Lysine methylation regulates the pRb tumour suppressor protein. Oncogene 29, 2357–2367 (2010).
  Article PubMed CAS Google Scholar
• Chan, H. M., Krstic-Demonacos, M., Smith, L., Demonacos, C. & La Thangue, N. B. Acetylation control of the retinoblastoma tumour-suppressor protein. Nat. Genet. 3, 667–674 (2001).
  CAS Google Scholar
• Hirschi, A. et al. An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein. Nat. Struct. Mol. Biol. 17, 1051–1057 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Julian, L. M., Palander, O., Seifried, L. A., Foster, J. E. & Dick, F. A. Characterization of an E2F1-specific binding domain in pRB and its implications for apoptotic regulation. Oncogene 27, 1572–1579 (2008).
  Article PubMed CAS Google Scholar
• Rubin, S. M., Gall, A. L., Zheng, N. & Pavletich, N. P. Structure of the Rb C-terminal domain bound to E2F1-DP1: a mechanism for phosphorylation-induced E2F release. Cell 123, 1093–1106 (2005).
  Article PubMed CAS Google Scholar
• Calbo, J. et al. G1 cyclin/cyclin-dependent kinase-coordinated phosphorylation of endogenous pocket proteins differentially regulates their interactions with E2F4 and E2F1 and gene expression. J. Biol. Chem. 277, 50263–50274 (2002).
  Article PubMed CAS Google Scholar
• Liban, T. J. et al. Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family. Proc. Natl Acad. Sci. USA 114, 4942–4947 (2017).
  Article PubMed PubMed Central CAS Google Scholar
• Cecchini, M. J. et al. A retinoblastoma allele that is mutated at its common E2F interaction site inhibits cell proliferation in gene targeted mice. Mol. Cell. Biol. 34, 2029–2045 (2014).
  Article PubMed PubMed Central CAS Google Scholar
• Dick, F. A. & Dyson, N. pRB contains an E2F1-specific binding domain that allows E2F1-induced apoptosis to be regulated separately from other E2F activities. Mol. Cell 12, 639–649 (2003).
  Article PubMed CAS Google Scholar
• Gubern, A. et al. The N-terminal phosphorylation of RB by p38 bypasses its inactivation by CDKs and prevents proliferation in cancer cells. Mol. Cell 64, 25–36 (2016).
  Article PubMed CAS Google Scholar
• Zhang, J. et al. Inhibition of Rb phosphorylation leads to mTORC2-mediated activation of Akt. Mol. Cell 62, 929–942 (2016).
  Article PubMed PubMed Central CAS Google Scholar
• Julian, L. M. et al. Opposing regulation of Sox2 by cell-cycle effectors E2f3a and E2f3b in neural stem cells. Cell Stem Cell 12, 440–452 (2013).
  Article PubMed CAS Google Scholar
• Alabert, C. & Groth, A. Chromatin replication and epigenome maintenance. Nat. Rev. Mol. Cell Biol. 13, 153–167 (2012).
  Article PubMed CAS Google Scholar
• Alabert, C. et al. Two distinct modes for propagation of histone PTMs across the cell cycle. Genes Dev. 29, 585–590 (2015).
  Article PubMed PubMed Central CAS Google Scholar
• Calo, E. et al. Rb regulates fate choice and lineage commitment in vivo. Nature 466, 1110–1114 (2010).
  Article PubMed PubMed Central Google Scholar
• Blais, A. & Dynlacht, B. D. E2F-associated chromatin modifiers and cell cycle control. Curr. Opin. Cell Biol. 19, 658–662 (2007).
  Article PubMed PubMed Central CAS Google Scholar
• Cook, R. et al. Direct involvement of retinoblastoma family proteins in DNA repair by non-homologous end-joining. Cell Rep 10, 2006–2018 (2015).
  Article PubMed PubMed Central CAS Google Scholar
• Velez-Cruz, R. et al. RB localizes to DNA double-strand breaks and promotes DNA end resection and homologous recombination through the recruitment of BRG1. Genes Dev. 30, 2500–2512 (2016).
  Article PubMed PubMed Central CAS Google Scholar
• Coschi, C. et al. Haploinsufficiency of an RB-E2F1-Condensin II complex leads to aberrant replication and aneuploidy. Cancer Discov. 4, 840–853 (2014).
  Article PubMed CAS Google Scholar
• Montoya-Durango, D. E. et al. Epigenetic control of mammalian LINE-1 retrotransposon by retinoblastoma proteins. Mutat. Res. 665, 20–28 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Chen, J. et al. E2F1 promotes the recruitment of DNA repair factors to sites of DNA double-strand breaks. Cell Cycle 10, 1287–1294 (2011).
  Article PubMed PubMed Central CAS Google Scholar
• Saddic, L. A. et al. Methylation of the retinoblastoma tumor suppressor by SMYD2. J. Biol. Chem. 285, 37733–37740 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Carnevale, J., Palander, O., Seifried, L. A. & Dick, F. A. DNA damage signals through differentially modified E2F1 molecules to induce apoptosis. Mol. Cell. Biol. 32, 900–912 (2012).
  Article PubMed PubMed Central CAS Google Scholar
• Chong, J. L. et al. E2f1-3 switch from activators in progenitor cells to repressors in differentiating cells. Nature 462, 930–934 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Yamasaki, L. et al. Tumor induction and tissue atrophy in mice lacking E2F-1. Cell 85, 537–548 (1996).
  Article PubMed CAS Google Scholar
• Chen, H. Z., Tsai, S. Y. & Leone, G. Emerging roles of E2Fs in cancer: an exit from cell cycle control. Nat. Rev. Cancer 9, 785–797 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Biedermann, S. et al. The retinoblastoma homolog RBR1 mediates localization of the repair protein RAD51 to DNA lesions in Arabidopsis. EMBO J. 36, 1279–1297 (2017).
  Article PubMed PubMed Central CAS Google Scholar
• Horvath, B. M. et al. Arabidopsis RETINOBLASTOMA RELATED directly regulates DNA damage responses through functions beyond cell cycle control. EMBO J. 36, 1261–1278 (2017).
  Article PubMed PubMed Central CAS Google Scholar
• Montoya-Durango, D. E. et al. LINE-1 silencing by retinoblastoma proteins is effected through the nucleosomal and remodeling deacetylase multiprotein complex. BMC Cancer 16, 38 (2016).
  Article PubMed PubMed Central CAS Google Scholar
• Manning, A. L. et al. Suppression of genome instability in pRB-deficient cells by enhancement of chromosome cohesion. Mol. Cell 53, 993–1004 (2014).
  Article PubMed PubMed Central CAS Google Scholar
• Gonzalo, S. et al. Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat. Cell Biol. 7, 420–428 (2005).
  Article PubMed CAS Google Scholar
• Isaac, C. E. et al. The retinoblastoma protein regulates pericentric heterochromatin. Mol. Cell. Biol. 26, 3659–3671 (2006).
  Article PubMed PubMed Central CAS Google Scholar
• Longworth, M. S., Herr, A., Ji, J. Y. & Dyson, N. J. RBF1 promotes chromatin condensation through a conserved interaction with the Condensin II protein dCAP-D3. Genes Dev. 22, 1011–1024 (2008).
  Article PubMed PubMed Central CAS Google Scholar
• Woodward, J. et al. Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability. Genes Dev. 30, 2173–2186 (2016).
  Article PubMed PubMed Central CAS Google Scholar
• Lukas, J., Lukas, C. & Bartek, J. More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance. Nat. Cell Biol. 13, 1161–1169 (2011).
  Article PubMed CAS Google Scholar
• Mankouri, H. W., Huttner, D. & Hickson, I. D. How unfinished business from S-phase affects mitosis and beyond. EMBO J. 32, 2661–2671 (2013).
  Article PubMed PubMed Central CAS Google Scholar
• Munro, S. et al. Linker histone H1.2 directs genome-wide chromatin association of the retinoblastoma tumor suppressor protein and facilitates its function. Cell Rep 19, 2193–2201 (2017).
  Article PubMed PubMed Central CAS Google Scholar
• Zheng, L., Flesken-Nikitin, A., Chen, P. L. & Lee, W. H. Deficiency of Retinoblastoma gene in mouse embryonic stem cells leads to genetic instability. Cancer Res. 62, 2498–2502 (2002).
  PubMed CAS Google Scholar
• Coschi, C. H. et al. Mitotic chromosome condensation mediated by the retinoblastoma protein is tumor-suppressive. Genes Dev. 24, 1351–1363 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Conklin, J. F., Baker, J. & Sage, J. The RB family is required for the self-renewal and survival of human embryonic stem cells. Nat. Commun. 3, 1244 (2012).
  Article PubMed CAS Google Scholar
• Schvartzman, J. M., Sotillo, R. & Benezra, R. Mitotic chromosomal instability and cancer: mouse modelling of the human disease. Nat. Rev. Cancer 10, 102–115 (2010).
  Article PubMed PubMed Central CAS Google Scholar
• Sharma, A. et al. Retinoblastoma tumor suppressor status is a critical determinant of therapeutic response in prostate cancer cells. Cancer Res. 67, 6192–6203 (2007).
  Article PubMed PubMed Central CAS Google Scholar
• Varma, H. & Conrad, S. E. Reversal of an antiestrogen-mediated cell cycle arrest of MCF-7 cells by viral tumor antigens requires the retinoblastoma protein-binding domain. Oncogene 19, 4746–4753 (2000).
  Article PubMed CAS Google Scholar
• Mayhew, C. N. et al. Discrete signaling pathways participate in RB-dependent responses to chemotherapeutic agents. Oncogene 23, 4107–4120 (2004).
  Article PubMed CAS Google Scholar
• Zagorski, W. A., Knudsen, E. S. & Reed, M. F. Retinoblastoma deficiency increases chemosensitivity in lung cancer. Cancer Res. 67, 8264–8273 (2007).
  Article PubMed CAS Google Scholar
• Bourgo, R. J. et al. RB restricts DNA damage-initiated tumorigenesis through an LXCXE-dependent mechanism of transcriptional control. Mol. Cell 43, 663–672 (2011).
  Article PubMed PubMed Central CAS Google Scholar
• Xiao, H. & Goodrich, D. W. The retinoblastoma tumor suppressor protein is required for efficient processing and repair of trapped topoisomerase II-DNA-cleavable complexes. Oncogene 24, 8105–8113 (2005).
  Article PubMed PubMed Central CAS Google Scholar
• The Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543–550 (2014).
  Article PubMed Central CAS Google Scholar
• Branzei, D. & Foiani, M. Regulation of DNA repair throughout the cell cycle. Nat. Rev. Mol. Cell Biol. 9, 297–308 (2008).
  Article PubMed CAS Google Scholar
• Sherr, C. J., Beach, D. & Shapiro, G. I. Targeting CDK4 and CDK6: from discovery to therapy. Cancer Discov. 6, 353–367 (2016).
  Article PubMed CAS Google Scholar
• Koh, J., Enders, G. H., Dynlacht, B. D. & Harlow, E. Tumor-derived p16 alleles encoding proteins defective in cell cycle inhibition. Nature 375, 506–510 (1995).
  Article PubMed CAS Google Scholar
• Lukas, J. et al. Retinoblastoma-protein-dependent inhibition by the tumor-suppressor p16. Nature 375, 503–506 (1995).
  Article PubMed CAS Google Scholar
• Bruce, J. L., Hurford, R. K. J., Classon, M., Koh, J. & Dyson, N. Requirements for cell cycle arrest by p16INK4a. Mol. Cell 6, 737–742 (2000).
  Article PubMed CAS Google Scholar
• Watson, P. A., Arora, V. K. & Sawyers, C. L. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer. Nat. Rev. Cancer 15, 701–711 (2015).
  Article PubMed PubMed Central CAS Google Scholar
• Tran, C. et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324, 787–790 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Rickman, D. S., Beltran, H., Demichelis, F. & Rubin, M. A. Biology and evolution of poorly differentiated neuroendocrine tumors. Nat. Med. 23, 1–10 (2017).
  Article PubMed CAS Google Scholar
• Bluemn, E. G. et al. Androgen receptor pathway-independent prostate cancer is sustained through FGF signaling. Cancer Cell 32, 474–489 (2017).
  Article PubMed CAS PubMed Central Google Scholar
• The Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer. Cell 163, 1011–1025 (2015).
  Article PubMed Central CAS Google Scholar
• Mu, P. et al. SOX2 promotes lineage plasticity and antiandrogen resistance in TP53- and RB1-deficient prostate cancer. Science 355, 84–88 (2017).
  Article PubMed PubMed Central CAS Google Scholar
• Ku, S. Y. et al. Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance. Science 355, 78–83 (2017).
  Article PubMed PubMed Central CAS Google Scholar
• Wang, S. et al. Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4, 209–221 (2003).
  Article PubMed CAS Google Scholar
• Zhou, Z. et al. Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 66, 7889–7898 (2006).
  Article PubMed CAS Google Scholar
• Maddison, L. A., Sutherland, B. W., Barrios, R. J. & Greenberg, N. M. Conditional deletion of Rb causes early stage prostate cancer. Cancer Res. 64, 6018–6025 (2004).
  Article PubMed CAS Google Scholar
• Lynch, T. J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129–2139 (2004).
  Article PubMed CAS Google Scholar
• Kobayashi, S. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352, 786–792 (2005).
  Article PubMed CAS Google Scholar
• Yun, C. H. et al. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell 11, 217–227 (2007).
  Article PubMed PubMed Central CAS Google Scholar
• Pirker, R. Third-generation epidermal growth factor receptor tyrosine kinase inhibitors in advanced nonsmall cell lung cancer. Curr. Opin. Oncol. 28, 115–121 (2016).
  Article PubMed CAS Google Scholar
• Sequist, L. V. et al. Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors. Sci. Transl Med. 3, 75ra26 (2011).
  Article PubMed PubMed Central Google Scholar
• Oser, M. G., Niederst, M. J., Sequist, L. V. & Engelman, J. A. Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin. Lancet Oncol. 16, e165–e172 (2015).
  Article PubMed PubMed Central CAS Google Scholar
• George, J. et al. Comprehensive genomic profiles of small cell lung cancer. Nature 524, 47–53 (2015).
  Article PubMed PubMed Central CAS Google Scholar
• Niederst, M. J. et al. RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer. Nat. Commun. 6, 6377 (2015).
  Article PubMed CAS Google Scholar
• Rothenberg, S. M. et al. Inhibition of mutant EGFR in lung cancer cells triggers SOX2-FOXO6-dependent survival pathways. eLife 4, e06132 (2015).
  Article PubMed Central CAS Google Scholar
• Ting, D. T. et al. Aberrant overexpression of satellite repeats in pancreatic and other epithelial cancers. Science 331, 593–596 (2011).
  Article PubMed PubMed Central CAS Google Scholar
• Liu, Y. et al. Mouse fibroblasts lacking RB1 function form spheres and undergo reprogramming to a cancer stem cell phenotype. Cell Stem Cell 4, 336–347 (2009).
  Article PubMed PubMed Central CAS Google Scholar
• Akamatsu, S. et al. The placental gene PEG10 promotes progression of neuroendocrine prostate cancer. Cell Rep. 12, 922–936 (2015).
  Article PubMed CAS Google Scholar
• Herrera-Merchan, A. et al. Ectopic expression of the histone methyltransferase Ezh2 in haematopoietic stem cells causes myeloproliferative disease. Nat. Commun. 3, 623 (2012).
  Article PubMed CAS Google Scholar
• Gonzalez-Vasconcellos, I. et al. Rb1 haploinsufficiency promotes telomere attrition and radiation-induced genomic instability. Cancer Res. 73, 4247–4255 (2013).
  Article PubMed CAS Google Scholar
• Hilgendorf, K. I. et al. The retinoblastoma protein induces apoptosis directly at the mitochondria. Genes Dev. 27, 1003–1015 (2013).
  Article PubMed PubMed Central CAS Google Scholar
• Araki, K., Kawauchi, K., Hirata, H., Yamamoto, M. & Taya, Y. Cytoplasmic translocation of the retinoblastoma protein disrupts sarcomeric organization. eLife 2, e01228 (2013).
  Article PubMed PubMed Central CAS Google Scholar
• Weinberg, R. A. The retinoblastoma protein and cell cycle control. Cell 81, 323–330 (1995).
  Article PubMed CAS Google Scholar
• The Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487, 330–337 (2012).
  Article CAS Google Scholar
• Ciriello, G. et al. Comprehensive molecular portraits of invasive lobular breast cancer. Cell 163, 506–519 (2015).
  Article PubMed PubMed Central CAS Google Scholar