Synthetic vulnerabilities of mesenchymal subpopulations in pancreatic cancer

Nature

Volumn 542, Issue 7641, 2017, Pages 362-366

  Genovese, Giannicola ^a   Carugo, Alessandro ^a,b   Tepper, James ^a   Robinson, Frederick Scott ^a   Li, Liren ^a,c   Svelto, Maria ^a,d   Nezi, Luigi ^a   Corti, Denise ^a   Minelli, Rosalba ^a   Pettazzoni, Piergiorgio ^a   Gutschner, Tony ^a   Wu, Chia Chin ^a   Seth, Sahil ^a   Akdemir, Kadir Caner ^a   Leo, Elisabetta ^a   Amin, Samirkumar ^a,e   Molin, Marco Dal ^f   Ying, Haoqiang ^a   Kwong, Lawrence N ^a   Colla, Simona ^a   Takahashi, Koichi ^a   Ghosh, Papia ^a   Giuliani, Virginia ^a   Muller, Florian ^a   Dey, Prasenjit ^a   Jiang, Shan ^a   Garvey, Jill ^a   Liu, Chang Gong ^a   Zhang, Jianhua ^a   Heffernan, Timothy P ^a,i   Toniatti, Carlo ^a   Fleming, Jason B ^a   Goggins, Michael G ^f   Wood, Laura D ^f   Sgambato, Alessandro ^d   Agaimy, Abbas ^g   Maitra, Anirban ^a   Roberts, Charles W M ^h   Wang, Huamin ^a   Viale, Andrea ^a   DePinho, Ronald A ^a   Draetta, Giulio F ^a   Chin, Lynda ^a,j   more..

^a UNIVERSITY OF TEXAS   (United States)

^b EUROPEAN INSTITUTE OF ONCOLOGY   (Italy)

^c SUN YAT SEN UNIVERSITY CANCER CENTER   (China)

^d CATHOLIC UNIVERSITY   (Italy)

^e BAYLOR COLLEGE OF MEDICINE   (United States)

^f JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g UNIVERSITY HOSPITAL ERLANGEN   (Germany)

^h ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

ⁱ C4 Therapeutics ^*  (United States)

^j UNIVERSITY OF TEXAS   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

CANCER; CELLS AND CELL COMPONENTS; CHEMORECEPTION; EXTINCTION; METABOLISM; MORPHOLOGY; PHENOTYPE; PROTEIN; RODENT; SUBPOPULATION; TUMOR; VULNERABILITY;

ARTICLE; CANCER CELL; CANCER PROGNOSIS; CARCINOGENESIS; CELL PLASTICITY; CELL SUBPOPULATION; ENDOPLASMIC RETICULUM STRESS; EPITHELIAL MESENCHYMAL TRANSITION; FLUORESCENCE ACTIVATED CELL SORTING; HUMAN; NONHUMAN; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN METABOLISM; PROTEIN SYNTHESIS; RNA INTERFERENCE; TUMOR GROWTH; UNFOLDED PROTEIN RESPONSE; ANALOGS AND DERIVATIVES; ANIMAL; CARCINOMA, PANCREATIC DUCTAL; DEFICIENCY; FEMALE; GENETICS; MALE; MESODERM; METABOLISM; MOSAICISM; MOUSE; ONCOGENE MYC; ONCOGENE RAS; PANCREATIC NEOPLASMS; PATHOLOGY; PROTEIN DEGRADATION; SIGNAL TRANSDUCTION;

DEOXYCYTIDINE; GEMCITABINE; MAP2K4 PROTEIN, HUMAN; MITOGEN ACTIVATED PROTEIN KINASE KINASE 4; ONCOPROTEIN; PROTEIN P21; SMARCB1 PROTEIN, MOUSE; SWI/SNF RELATED MATRIX ASSOCIATED ACTIN DEPENDENT REGULATOR OF CHROMATIN SUBFAMILY B MEMBER 1; TRANSCRIPTOME;

ANIMALS; CARCINOMA, PANCREATIC DUCTAL; DEOXYCYTIDINE; ENDOPLASMIC RETICULUM STRESS; FEMALE; GENES, MYC; GENES, RAS; HUMANS; MALE; MAP KINASE KINASE 4; MAP KINASE SIGNALING SYSTEM; MESODERM; MICE; MOSAICISM; ONCOGENE PROTEIN P55(V-MYC); PANCREATIC NEOPLASMS; PROTEOLYSIS; PROTO-ONCOGENE PROTEINS P21(RAS); SMARCB1 PROTEIN; TRANSCRIPTOME;

EID: 85014650754     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature21064     Document Type: Article

References (58)

1. Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell 144, 646-674 (2011).
2. Nieto, M. A., Huang, R. Y., Jackson, R. A. & Thiery, J. P. Emt: 2016. Cell 166, 21-45 (2016).
3. Pisco, A. O. & Huang, S. Non-genetic cancer cell plasticity and therapy-induced stemness in tumour relapse: 'What does not kill me strengthens me'. Br. J. Cancer 112, 1725-1732 (2015).
4. Rhim, A. D. et al. EMT and dissemination precede pancreatic tumor formation. Cell 148, 349-361 (2012).
5. Kopp, J. L. et al. Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell 22, 737-750 (2012).
6. Morris, J. P., IV, Cano, D. A., Sekine, S., Wang, S. C. & Hebrok, M. β-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. J. Clin. Invest. 120, 508-520 (2010).
7. Lee, K. E. & Bar-Sagi, D. Oncogenic KRas suppresses inflammationassociated senescence of pancreatic ductal cells. Cancer Cell 18, 448-458 (2010).
8. Reichert, M. et al. Isolation, culture and genetic manipulation of mouse pancreatic ductal cells. Nat. Protocols 8, 1354-1365 (2013).
9. Isakoff, M. S. et al. Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation. Proc. Natl Acad. Sci. USA 102, 17745-17750 (2005).
10. Barbie, D. A. et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature 462, 108-112 (2009).
11. Creighton, C. J. et al. Activation of mitogen-activated protein kinase in estrogen receptor α-positive breast cancer cells in vitro induces an in vivo molecular phenotype of estrogen receptor a-negative human breast tumors. Cancer Res. 66, 3903-3911 (2006).
12. Ma, Y., Croxton, R., Moorer, R. L., Jr & Cress, W. D. Identification of novel E2F1-regulated genes by microarray. Arch. Biochem. Biophys. 399, 212-224 (2002).
13. Chiou, S. H. et al. Pancreatic cancer modeling using retrograde viral vector delivery and in vivo CRISPR/Cas9-mediated somatic genome editing. Genes Dev. 29, 1576-1585 (2015).
14. Collisson, E. A. et al. Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nat. Med. 17, 500-503 (2011).
15. Noll, E. M. et al. CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma. Nat. Med. 22, 278-287 (2016).
16. Signer, R. A., Magee, J. A., Salic, A. & Morrison, S. J. Haematopoietic stem cells require a highly regulated protein synthesis rate. Nature 509, 49-54 (2014).
17. Hart, L. S. et al. ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth. J. Clin. Invest. 122, 4621-4634 (2012).
18. Lin, J. H. et al. IRE1 signaling affects cell fate during the unfolded protein response. Science 318, 944-949 (2007).
19. Urano, F. et al. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 287, 664-666 (2000).
20. Chen, Y. & Brandizzi, F. IRE1: ER stress sensor and cell fate executor. Trends Cell Biol. 23, 547-555 (2013).
21. Chien, W. et al. Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cells. Oncotarget 5, 4881-4894 (2014).
22. Gao, H. et al. High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response. Nat. Med. 21, 1318-1325 (2015).
23. Siolas, D. & Hannon, G. J. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res. 73, 5315-5319 (2013).
24. Aparicio, S., Hidalgo, M. & Kung, A. L. Examining the utility of patient-derived xenograft mouse models. Nat. Rev. Cancer 15, 311-316 (2015).
25. Carugo, A. et al. In vivo functional platform targeting patient-derived xenografts identifies WDR5-Myc association as a critical determinant of pancreatic cancer. Cell Reports 16, 133-147 (2016).
26. Singh, A. et al. A gene expression signature associated with "K-Ras addiction" reveals regulators of EMT and tumor cell survival. Cancer Cell 15, 489-500 (2009).
27. Agaimy, A. The expanding family of SMARCB1(INI1)-deficient neoplasia: implications of phenotypic, biological, and molecular heterogeneity. Adv. Anat. Pathol. 21, 394-410 (2014).
28. Agaimy, A., Rau, T. T., Hartmann, A. & Stoehr, R. SMARCB1 (INI1)-negative rhabdoid carcinomas of the gastrointestinal tract: clinicopathologic and molecular study of a highly aggressive variant with literature review. Am. J. Surg. Pathol. 38, 910-920 (2014).
29. Agaimy, A. et al. Pancreatic undifferentiated rhabdoid carcinoma: KRAS alterations and SMARCB1 expression status define two subtypes. Mod. Pathol. 28, 248-260 (2015).
30. Ventura, A. et al. Restoration of p53 function leads to tumour regression in vivo. Nature 445, 661-665 (2007).
31. Young, N. P. & Jacks, T. Tissue-specific p19Arf regulation dictates the response to oncogenic K-ras. Proc. Natl Acad. Sci. USA 107, 10184-10189 (2010).
32. Jackson, E. L. et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15, 3243-3248 (2001).
33. Cheung, A. F., Dupage, M. J., Dong, H. K., Chen, J. & Jacks, T. Regulated expression of a tumor-associated antigen reveals multiple levels of T-cell tolerance in a mouse model of lung cancer. Cancer Res. 68, 9459-9468 (2008).
34. Lee, C. L. et al. Generation of primary tumors with Flp recombinase in FRT-flanked p53 mice. Dis. Model. Mech. 5, 397-402 (2012).
35. Muzumdar, M. D., Tasic, B., Miyamichi, K., Li, L. & Luo, L. A global doublefluorescent Cre reporter mouse. Genesis 45, 593-605 (2007).
36. Roberts, C. W., Leroux, M. M., Fleming, M. D. & Orkin, S. H. Highly penetrant, rapid tumorigenesis through conditional inversion of the tumor suppressor gene Snf5. Cancer Cell 2, 415-425 (2002).
37. Hingorani, S. R. et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 4, 437-450 (2003).
38. Marino, S., Vooijs, M., van Der Gulden, H., Jonkers, J. & Berns, A. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev. 14, 994-1004 (2000).
39. Kawaguchi, Y. et al. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat. Genet. 32, 128-134 (2002).
40. Lao, Z., Raju, G. P., Bai, C. B. & Joyner, A. L. MASTR: a technique for mosaic mutant analysis with spatial and temporal control of recombination using conditional floxed alleles in mice. Cell Rep. 2, 386-396 (2012).
41. Snippert, H. J. et al. Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell 143, 134-144 (2010).
42. Kissler, S. et al. In vivo RNA interference demonstrates a role for Nramp1 in modifying susceptibility to type 1 diabetes. Nat. Genet. 38, 479-483 (2006).
43. Ventura, A. et al. Cre-lox-regulated conditional RNA interference from transgenes. Proc. Natl Acad. Sci. USA 101, 10380-10385 (2004).
44. Koo, B. K. et al. Controlled gene expression in primary Lgr5 organoid cultures. Nat. Methods 9, 81-83 (2011).
45. Campeau, E. et al. A versatile viral system for expression and depletion of proteins in mammalian cells. PLoS One 4, e6529 (2009).
46. Young, N. P., Crowley, D. & Jacks, T. Uncoupling cancer mutations reveals critical timing of p53 loss in sarcomagenesis. Cancer Res. 71, 4040-4047 (2011).
47. Genovese, G. et al. microRNA regulatory network inference identifies miR-34a as a novel regulator of TGF-β signaling in glioblastoma. Cancer Discov. 2, 736-749 (2012).
48. Winslow, M. M. et al. Suppression of lung adenocarcinoma progression by Nkx2-1. Nature 473, 101-104 (2011).
49. Beerling, E. et al. Plasticity between epithelial and mesenchymal states unlinks emt from metastasis-enhancing stem cell capacity. Cell Reports 14, 2281-2288 (2016).
50. Kim, M. P. et al. Molecular profiling of direct xenograft tumors established from human pancreatic adenocarcinoma after neoadjuvant therapy. Ann. Surg. Oncol. 19 (Suppl. 3), S395-S403 (2012).
51. Kim, M. P. et al. Generation of orthotopic and heterotopic human pancreatic cancer xenografts in immunodeficient mice. Nat. Protocols 4, 1670-1680 (2009).
52. Viale, A. et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature 514, 628-632 (2014).
53. Agbunag, C., Lee, K. E., Buontempo, S. & Bar-Sagi, D. Pancreatic duct epithelial cell isolation and cultivation in two-dimensional and three-dimensional culture systems. Methods Enzymol. 407, 703-710 (2006).
54. Rudalska, R. et al. In vivo RNAi screening identifies a mechanism of sorafenib resistance in liver cancer. Nat. Med. 20, 1138-1146 (2014).
55. Quintana, E. et al. Efficient tumour formation by single human melanoma cells. Nature 456, 593-598 (2008).
56. Bonnefoix, T., Bonnefoix, P., Verdiel, P. & Sotto, J. J. Fitting limiting dilution experiments with generalized linear models results in a test of the single-hit Poisson assumption. J. Immunol. Methods 194, 113-119 (1996).
57. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545-15550 (2005).
58. Ashburner, M. et al. The Gene Ontology Consortium. Gene ontology: tool for the unification of biology. Nat. Genet. 25, 25-29 (2000).