An essential role for Argonaute 2 in EGFR-KRAS signaling in pancreatic cancer development.

Alleles Animals Argonaute Proteins / metabolism Cell Line, Tumor Cell Membrane / metabolism Cellular Senescence Disease Progression ErbB Receptors / metabolism Female Gene Expression Regulation, Neoplastic Genotype Humans Male Mice Mice, Transgenic Neoplasm Transplantation Pancreatic Neoplasms / metabolism Phosphorylation Protein Binding Proto-Oncogene Proteins p21(ras) / metabolism Signal Transduction Tumor Suppressor Protein p53 / metabolism

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
04 06 2020
Historique:
received: 26 07 2019
accepted: 20 04 2020
entrez: 6 6 2020
pubmed: 6 6 2020
medline: 19 8 2020
Statut: epublish

Résumé

Both KRAS and EGFR are essential mediators of pancreatic cancer development and interact with Argonaute 2 (AGO2) to perturb its function. Here, in a mouse model of mutant KRAS-driven pancreatic cancer, loss of AGO2 allows precursor lesion (PanIN) formation yet prevents progression to pancreatic ductal adenocarcinoma (PDAC). Precursor lesions with AGO2 ablation undergo oncogene-induced senescence with altered microRNA expression and EGFR/RAS signaling, bypassed by loss of p53. In mouse and human pancreatic tissues, PDAC progression is associated with increased plasma membrane localization of RAS/AGO2. Furthermore, phosphorylation of AGO2

Identifiants

DOI: 10.1038/s41467-020-16309-2 PMID: 32499547 PMC: PMC7272436
pubmed: 32499547
doi: 10.1038/s41467-020-16309-2
pii: 10.1038/s41467-020-16309-2
pmc: PMC7272436
doi:

Substances chimiques

AGO2 protein, human 0
Ago2 protein, mouse 0
Argonaute Proteins 0
KRAS protein, human 0
TP53 protein, human 0
Tumor Suppressor Protein p53 0
EGFR protein, human EC 2.7.10.1
EGFR protein, mouse EC 2.7.10.1
ErbB Receptors EC 2.7.10.1
Hras protein, mouse EC 3.6.5.2
Proto-Oncogene Proteins p21(ras) EC 3.6.5.2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

2817

Subventions

Organisme : NCI NIH HHS
ID : R35 CA231996
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA224145
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007315
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007863
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA234222
Pays : United States

Références

Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin. 69, 7–34 (2019).
pubmed: 30620402 pmcid: 30620402 doi: 10.3322/caac.21551
Simanshu, D. K., Nissley, D. V. & McCormick, F. RAS proteins and their regulators in human disease. Cell 170, 17–33 (2017).
pubmed: 28666118 pmcid: 5555610 doi: 10.1016/j.cell.2017.06.009
Pylayeva-Gupta, Y., Grabocka, E. & Bar-Sagi, D. RAS oncogenes: weaving a tumorigenic web. Nat. Rev. Cancer 11, 761–774 (2011).
pubmed: 21993244 pmcid: 3632399 doi: 10.1038/nrc3106
Hingorani, S. R. et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 4, 437–450 (2003).
pubmed: 14706336 doi: 10.1016/S1535-6108(03)00309-X
Herreros-Villanueva, M., Hijona, E., Cosme, A. & Bujanda, L. Mouse models of pancreatic cancer. World J. Gastroenterol. 18, 1286–1294 (2012).
pubmed: 22493542 pmcid: 3319955 doi: 10.3748/wjg.v18.i12.1286
Drosten, M., Guerra, C. & Barbacid, M. Genetically engineered mouse models of K-Ras-driven lung and pancreatic tumors: validation of therapeutic targets. Cold Spring Harb. Perspect. Med. 8, 1–18 (2018).
doi: 10.1101/cshperspect.a031542
Ardito, C. M. et al. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell 22, 304–317 (2012).
pubmed: 22975374 pmcid: 3443395 doi: 10.1016/j.ccr.2012.07.024
Navas, C. et al. EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal adenocarcinoma. Cancer Cell 22, 318–330 (2012).
pubmed: 22975375 pmcid: 3601542 doi: 10.1016/j.ccr.2012.08.001
Wang, J. P. et al. Erlotinib is effective in pancreatic cancer with epidermal growth factor receptor mutations: a randomized, open-label, prospective trial. Oncotarget 6, 18162–18173 (2015).
pubmed: 26046796 pmcid: 4627242 doi: 10.18632/oncotarget.4216
McCormick, F. KRAS as a therapeutic target. Clin. Cancer Res. 21, 1797–1801 (2015).
pubmed: 25878360 pmcid: 4407814 doi: 10.1158/1078-0432.CCR-14-2662
Shankar, S. et al. KRAS engages AGO2 to enhance cellular transformation. Cell Rep. 14, 1448–1461 (2016).
pubmed: 26854235 pmcid: 4758864 doi: 10.1016/j.celrep.2016.01.034
Shen, J. et al. EGFR modulates microRNA maturation in response to hypoxia through phosphorylation of AGO2. Nature 497, 383–387 (2013).
pubmed: 23636329 pmcid: 3717558 doi: 10.1038/nature12080
O’Carroll, D. et al. A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev. 21, 1999–2004 (2007).
pubmed: 17626790 pmcid: 1948855 doi: 10.1101/gad.1565607
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).
pubmed: 23201164 pmcid: 3568632 doi: 10.1016/j.ccr.2012.10.025
Qiu, W. et al. Disruption of p16 and activation of Kras in pancreas increase ductal adenocarcinoma formation and metastasis in vivo. Oncotarget 2, 862–873 (2011).
pubmed: 22113502 pmcid: 3259996 doi: 10.18632/oncotarget.357
Morris, J. P. T. et al. Dicer regulates differentiation and viability during mouse pancreatic cancer initiation. PLoS ONE 9, e95486 (2014).
pubmed: 24788257 pmcid: 4006805 doi: 10.1371/journal.pone.0095486
Hingorani, S. R. et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7, 469–483 (2005).
pubmed: 15894267 doi: 10.1016/j.ccr.2005.04.023
Guerra, C. & Barbacid, M. Genetically engineered mouse models of pancreatic adenocarcinoma. Mol. Oncol. 7, 232–247 (2013).
pubmed: 23506980 pmcid: 5528418 doi: 10.1016/j.molonc.2013.02.002
Collins, M. A. et al. Metastatic pancreatic cancer is dependent on oncogenic Kras in mice. PLoS ONE 7, e49707 (2012).
pubmed: 23226501 pmcid: 3513322 doi: 10.1371/journal.pone.0049707
Caldwell, M. E. et al. Cellular features of senescence during the evolution of human and murine ductal pancreatic cancer. Oncogene 31, 1599–1608 (2012).
pubmed: 21860420 doi: 10.1038/onc.2011.350 pmcid: 21860420
Collisson, E. A. et al. A central role for RAF–>MEK–>ERK signaling in the genesis of pancreatic ductal adenocarcinoma. Cancer Discov. 2, 685–693 (2012).
pubmed: 22628411 pmcid: 3425446 doi: 10.1158/2159-8290.CD-11-0347
Sun, J. C. & Lanier, L. L. NK cell development, homeostasis and function: parallels with CD8(+) T cells. Nat. Rev. Immunol. 11, 645–657 (2011).
pubmed: 21869816 pmcid: 21869816 doi: 10.1038/nri3044
Krizhanovsky, V. et al. Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology. Cold Spring Harb. Symp. Quant. Biol. 73, 513–522 (2008).
pubmed: 19150958 doi: 10.1101/sqb.2008.73.048
Krizhanovsky, V. et al. Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657–667 (2008).
pubmed: 18724938 pmcid: 3073300 doi: 10.1016/j.cell.2008.06.049
Morton, J. P. et al. Mutant p53 drives metastasis and overcomes growth arrest/senescence in pancreatic cancer. Proc. Natl Acad. Sci. USA 107, 246–251 (2010).
pubmed: 20018721 doi: 10.1073/pnas.0908428107
Jones, S. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801–1806 (2008).
pubmed: 18772397 pmcid: 2848990 doi: 10.1126/science.1164368
Maitra, A., Fukushima, N., Takaori, K. & Hruban, R. H. Precursors to invasive pancreatic cancer. Adv. Anat. Pathol. 12, 81–91 (2005).
pubmed: 15731576 doi: 10.1097/01.pap.0000155055.14238.25
Schmick, M. et al. KRas localizes to the plasma membrane by spatial cycles of solubilization, trapping and vesicular transport. Cell 157, 459–471 (2014).
pubmed: 24725411 pmcid: 24725411 doi: 10.1016/j.cell.2014.02.051
Waters, A. M. et al. Evaluation of the selectivity and sensitivity of isoform- and mutation-specific RAS antibodies. Sci. Signal 10, eaao3332 (2017).
pubmed: 28951536 pmcid: 5812265 doi: 10.1126/scisignal.aao3332
Chung, W. J. et al. Kras mutant genetically engineered mouse models of human cancers are genomically heterogeneous. Proc. Natl Acad. Sci. USA 114, E10947–E10955 (2017).
pubmed: 29203670 doi: 10.1073/pnas.1708391114
Halbrook, C. J. et al. Mitogen-activated protein kinase kinase activity maintains acinar-to-ductal metaplasia and is required for organ regeneration in pancreatitis. Cell Mol. Gastroenterol. Hepatol. 3, 99–118 (2017).
pubmed: 28090569 doi: 10.1016/j.jcmgh.2016.09.009
Gullberg, M. et al. Cytokine detection by antibody-based proximity ligation. Proc. Natl Acad. Sci. USA 101, 8420–8424 (2004).
pubmed: 15155907 doi: 10.1073/pnas.0400552101
Soderberg, O. et al. Direct observation of individual endogenous protein complexes in situ by proximity ligation. Nat. Methods 3, 995–1000 (2006).
pubmed: 17072308 doi: 10.1038/nmeth947
Martinez, I., Cazalla, D., Almstead, L. L., Steitz, J. A. & DiMaio, D. miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proc. Natl Acad. Sci. USA 108, 522–527 (2011).
pubmed: 21187425 doi: 10.1073/pnas.1017346108
Johnson, C. D. et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 67, 7713–7722 (2007).
pubmed: 17699775 doi: 10.1158/0008-5472.CAN-07-1083
Patranabis, S. & Bhattacharyya, S. N. Phosphorylation of Ago2 and subsequent inactivation of let-7a RNP-specific microRNAs control differentiation of mammalian sympathetic neurons. Mol. Cell Biol. 36, 1260–1271 (2016).
pubmed: 26858302 pmcid: 4836275 doi: 10.1128/MCB.00054-16
Ashton, T. M., McKenna, W. G., Kunz-Schughart, L. A. & Higgins, G. S. Oxidative phosphorylation as an emerging target in cancer therapy. Clin. Cancer Res. 24, 2482–2490 (2018).
pubmed: 29420223 doi: 10.1158/1078-0432.CCR-17-3070
Siveke, J. T. & Crawford, H. C. KRAS above and beyond - EGFR in pancreatic cancer. Oncotarget 3, 1262–1263 (2012).
pubmed: 23174662 pmcid: 3717786 doi: 10.18632/oncotarget.750
Boj, S. F. et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 160, 324–338 (2015).
pubmed: 25557080 doi: 10.1016/j.cell.2014.12.021
Oda, K., Matsuoka, Y., Funahashi, A. & Kitano, H. A comprehensive pathway map of epidermal growth factor receptor signaling. Mol. Syst. Biol. 1, 1–17 (2005).
doi: 10.1038/msb4100014
Lowenstein, E. J. et al. The Sh2 and Sh3 domain containing protein Grb2 links receptor tyrosine kinases to Ras signaling. Cell 70, 431–442 (1992).
pubmed: 1322798 doi: 10.1016/0092-8674(92)90167-B
Hayes, T. K. & Der, C. J. Mutant and wild-type Ras: co-conspirators in cancer. Cancer Discov. 3, 24–26 (2013).
pubmed: 23319767 doi: 10.1158/2159-8290.CD-12-0521
Young, A., Lou, D. & McCormick, F. Oncogenic and wild-type Ras play divergent roles in the regulation of mitogen-activated protein kinase signaling. Cancer Discov. 3, 112–123 (2013).
pubmed: 23103856 doi: 10.1158/2159-8290.CD-12-0231
Broderick, J. A., Salomon, W. E., Ryder, S. P., Aronin, N. & Zamore, P. D. Argonaute protein identity and pairing geometry determine cooperativity in mammalian RNA silencing. RNA 17, 1858–1869 (2011).
pubmed: 21878547 pmcid: 3185918 doi: 10.1261/rna.2778911
Tan, X., Lambert, P. F., Rapraeger, A. C. & Anderson, R. A. Stress-Induced EGFR Trafficking: Mechanisms, Functions, and Therapeutic Implications. Trends Cell Biol. 26, 352–366 (2016).
pubmed: 26827089 pmcid: 5120732 doi: 10.1016/j.tcb.2015.12.006
Janes, M. R. et al. Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor. Cell 172, 578–589 (2018).
pubmed: 29373830 doi: 10.1016/j.cell.2018.01.006
Lito, P., Solomon, M., Li, L. S., Hansen, R. & Rosen, N. Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism. Science 351, 604–608 (2016).
pubmed: 26841430 pmcid: 4955282 doi: 10.1126/science.aad6204
Perez-Mancera, P. A., Guerra, C., Barbacid, M. & Tuveson, D. A. What we have learned about pancreatic cancer from mouse models. Gastroenterology 142, 1079–1092 (2012).
pubmed: 22406637 doi: 10.1053/j.gastro.2012.03.002
Gutmann, D. H., Hunter-Schaedle, K. & Shannon, K. M. Harnessing preclinical mouse models to inform human clinical cancer trials. J. Clin. Invest, 116, 847–852 (2006).
doi: 10.1172/JCI28271
Sagiv, A. et al. Granule exocytosis mediates immune surveillance of senescent cells. Oncogene 32, 1971–1977 (2013).
pubmed: 22751116 doi: 10.1038/onc.2012.206
Lyu, G. et al. TGF-beta signaling alters H4K20me3 status via miR-29 and contributes to cellular senescence and cardiac aging. Nat. Commun. 9, 2560 (2018).
pubmed: 29967491 pmcid: 6028646 doi: 10.1038/s41467-018-04994-z
Hu, Z. et al. MicroRNA-29 induces cellular senescence in aging muscle through multiple signaling pathways. Aging 6, 160–175 (2014).
pubmed: 24659628 pmcid: 4012934 doi: 10.18632/aging.100643
Wang, X. et al. Regulation of let-7 and its target oncogenes (Review). Oncol. Lett. 3, 955–960 (2012).
pubmed: 22783372 pmcid: 3389667 doi: 10.3892/ol.2012.609
Balzeau, J., Menezes, M. R., Cao, S. & Hagan, J. P. The LIN28/let-7 pathway in cancer. Front. Genet. 8, 31 (2017).
pubmed: 28400788 pmcid: 5368188 doi: 10.3389/fgene.2017.00031
Kwon, J. J. et al. Novel role of miR-29a in pancreatic cancer autophagy and its therapeutic potential. Oncotarget 7, 71635–71650 (2016).
pubmed: 27626694 pmcid: 5342107 doi: 10.18632/oncotarget.11928
Dou, Z. et al. Autophagy mediates degradation of nuclear lamina. Nature 527, 105–109 (2015).
pubmed: 26524528 pmcid: 4824414 doi: 10.1038/nature15548
Kourtidis, A. & Anastasiadis, P. Z. Close encounters of the RNAi kind: the silencing life of the adherens junctions. Curr. Opin. Cell Biol. 54, 30–36 (2018).
pubmed: 29587176 pmcid: 6153086 doi: 10.1016/j.ceb.2018.03.001
Zeng, Y. & Cullen, B. R. RNA interference in human cells is restricted to the cytoplasm. RNA 8, 855–860 (2002).
pubmed: 12166640 pmcid: 1370302 doi: 10.1017/S1355838202020071
Stalder, L. et al. The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing. EMBO J. 32, 1115–1127 (2013).
pubmed: 23511973 pmcid: 3630355 doi: 10.1038/emboj.2013.52
Gagnon, K. T., Li, L., Chu, Y., Janowski, B. A. & Corey, D. R. RNAi factors are present and active in human cell nuclei. Cell Rep. 6, 211–221 (2014).
pubmed: 24388755 pmcid: 3916906 doi: 10.1016/j.celrep.2013.12.013
Moor, A. E. et al. Global mRNA polarization regulates translation efficiency in the intestinal epithelium. Science 357, 1299–1303 (2017).
pubmed: 28798045 pmcid: 5955215 doi: 10.1126/science.aan2399
Wee, P. & Wang, Z. X. Epidermal growth factor receptor cell proliferation signaling pathways. Cancers 9, 1–45 (2017).
Yang, M. et al. Dephosphorylation of tyrosine 393 in argonaute 2 by protein tyrosine phosphatase 1B regulates gene silencing in oncogenic RAS-induced senescence. Mol. Cell 55, 782–790 (2014).
pubmed: 25175024 pmcid: 4159145 doi: 10.1016/j.molcel.2014.07.018
Jee, D. & Lai, E. C. Alteration of miRNA activity via context-specific modifications of Argonaute proteins. Trends Cell Biol. 24, 546–553 (2014).
pubmed: 24865524 pmcid: 4149831 doi: 10.1016/j.tcb.2014.04.008
Kawaguchi, Y. et al. The role of the transcriptional regulator Ptf1a in converting intestinal to pancreatic progenitors. Nat. Genet 32, 128–134 (2002).
pubmed: 12185368 doi: 10.1038/ng959
Ettel, M., Zhao, L., Schechter, S. & Shi, J. Expression and prognostic value of NSD1 and SETD2 in pancreatic ductal adenocarcinoma and its precursor lesions. Pathology 51, 392–398 (2019).
pubmed: 31060750 doi: 10.1016/j.pathol.2019.02.005 pmcid: 6544165
Robinson, M. D. & Oshlack, A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 11, R25 (2010).
pubmed: 20196867 pmcid: 2864565 doi: 10.1186/gb-2010-11-3-r25
Smyth, G. K. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 3, Article 3 (2004).
doi: 10.2202/1544-6115.1027
Law, C. W., Chen, Y., Shi, W. & Smyth, G. K. voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 15, R29 (2014).
pubmed: 24485249 pmcid: 4053721 doi: 10.1186/gb-2014-15-2-r29
Heijmans, J. et al. ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response. Cell Rep. 3, 1128–1139 (2013).
pubmed: 23545496 doi: 10.1016/j.celrep.2013.02.031

Auteurs

Sunita Shankar (S)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Jean Ching-Yi Tien (JC)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Ronald F Siebenaler (RF)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
ORCID: 0000-0003-1583-1547

Seema Chugh (S)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Vijaya L Dommeti (VL)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Sylvia Zelenka-Wang (S)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Xiao-Ming Wang (XM)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Ingrid J Apel (IJ)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Jessica Waninger (J)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Sanjana Eyunni (S)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Alice Xu (A)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Malay Mody (M)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Andrew Goodrum (A)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Yuping Zhang (Y)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

John J Tesmer (JJ)

Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA.

Rahul Mannan (R)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Xuhong Cao (X)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, 48109, USA.

Pankaj Vats (P)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
ORCID: 0000-0001-8441-7732

Sethuramasundaram Pitchiaya (S)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
ORCID: 0000-0003-2529-5186

Stephanie J Ellison (SJ)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Jiaqi Shi (J)

Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Chandan Kumar-Sinha (C)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA.

Howard C Crawford (HC)

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, 48109, USA.
Internal Medicine, University of Michigan, Ann Arbor, MI, 48109, USA.

Arul M Chinnaiyan (AM)

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, 48109, USA. arul@umich.edu.
Department of Pathology, University of Michigan, Ann Arbor, MI, 48109, USA. arul@umich.edu.
Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, 48109, USA. arul@umich.edu.
Department of Urology, University of Michigan, Ann Arbor, MI, 48109, USA. arul@umich.edu.
Rogel Cancer Center, University of Michigan, Ann Arbor, MI, 48109, USA. arul@umich.edu.
ORCID: 0000-0001-8743-7480

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Classifications MeSH

questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Composants de génome › Gènes › Allèles › An essential role for Argonaute 2 in EGFR-KRAS...
questionsmedicales.fr › Eucaryotes › Animaux › An essential role for Argonaute 2 in EGFR-KRAS...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Nucléoprotéines › Protéines de liaison à l'ARN › Ribonucléoprotéines › Complexe réprimant l'expression de l'ARN › Protéines Argonaute › An essential role for Argonaute 2 in EGFR-KRAS...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › An essential role for Argonaute 2 in EGFR-KRAS...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › An essential role for Argonaute 2 in EGFR-KRAS...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Vieillissement de la cellule › An essential role for Argonaute 2 in EGFR-KRAS...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › An essential role for Argonaute 2 in EGFR-KRAS...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs peptidiques › Récepteur facteur croissance › Récepteurs ErbB › An essential role for Argonaute 2 in EGFR-KRAS...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › An essential role for Argonaute 2 in EGFR-KRAS...
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