DOCK6 promotes chemo- and radioresistance of gastric cancer by modulating WNT/β-catenin signaling and cancer stem cell traits.

Animals Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Disease Models, Animal Disease Progression Drug Resistance, Neoplasm / genetics Gene Expression Regulation, Neoplastic Gene Silencing Guanine Nucleotide Exchange Factors / genetics Heterografts Humans Immunohistochemistry Immunophenotyping Mice Neoplastic Stem Cells / metabolism Phenotype Radiation Tolerance / genetics Stomach Neoplasms / genetics Wnt Signaling Pathway

Journal

Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562

Informations de publication

Date de publication:
09 2020
Historique:
received: 14 04 2019
accepted: 07 07 2020
pubmed: 6 8 2020
medline: 1 12 2020
entrez: 6 8 2020
Statut: ppublish

Résumé

Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide and prognosis after potentially curative gastrectomy remains poor. Administration of GC-targeting molecules in combination with adjuvant chemo- or radiotherapy following surgical resection has been proposed as a potentially effective treatment option. Here, we have identified DOCK6, a guanine nucleotide exchange factor (GEF) for Rac1 and CDC42, as an independent biomarker for GC prognosis. Clinical findings indicate the positive correlation of higher DOCK6 expression with tumor size, depth of invasion, lymph node metastasis, vascular invasion, and pathological stage. Furthermore, elevated DOCK6 expression was significantly associated with shorter cumulative survival in both univariate and multivariate analyses. Gene ontology analysis of three independent clinical GC cohorts revealed significant involvement of DOCK6-correlated genes in the WNT/β-catenin signaling pathway. Ectopic expression of DOCK6 promoted GC cancer stem cell (CSC) characteristics and chemo- or radioresistance concomitantly through Rac1 activation. Conversely, depletion of DOCK6 suppressed CSC phenotypes and progression of GC, further demonstrating the pivotal role of DOCK6 in GC progression. Our results demonstrate a novel mechanistic link between DOCK6, Rac1, and β-catenin in GCCSC for the first time, supporting the utility of DOCK6 as an independent marker of GC.

Identifiants

DOI: 10.1038/s41388-020-01390-0 PMID: 32753649
pubmed: 32753649
doi: 10.1038/s41388-020-01390-0
pii: 10.1038/s41388-020-01390-0
doi:

Substances chimiques

DOCK6 protein, human 0
Guanine Nucleotide Exchange Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5933-5949

Références

Baniak N, Senger JL, Ahmed S, Kanthan SC, Kanthan R. Gastric biomarkers: a global review. World J Surg Oncol. 2016;14:212.
pubmed: 27514667 pmcid: 4982433 doi: 10.1186/s12957-016-0969-3
Tsai MM, Wang CS, Tsai CY, Huang CG, Lee KF, Huang HW, et al. Circulating microRNA-196a/b are novel biomarkers associated with metastatic gastric cancer. Eur J Cancer. 2016;64:137–48.
pubmed: 27420607 doi: 10.1016/j.ejca.2016.05.007
Kwon KJ, Shim KN, Song EM, Choi JY, Kim SE, Jung HK, et al. Clinicopathological characteristics and prognosis of signet ring cell carcinoma of the stomach. Gastric Cancer. 2014;17:43–53.
pubmed: 23389081 doi: 10.1007/s10120-013-0234-1
Dalerba P, Cho RW, Clarke MF. Cancer stem cells: models and concepts. Annu Rev Med. 2007;58:267–84.
pubmed: 17002552 doi: 10.1146/annurev.med.58.062105.204854
Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008;8:755–68.
pubmed: 18784658 doi: 10.1038/nrc2499
Takaishi S, Okumura T, Tu S, Wang SS, Shibata W, Vigneshwaran R, et al. Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009;27:1006–20.
pubmed: 19415765 pmcid: 2746367 doi: 10.1002/stem.30
Hoey T, Yen WC, Axelrod F, Basi J, Donigian L, Dylla S, et al. DLL4 blockade inhibits tumor growth and reduces tumor-initiating cell frequency. Cell Stem Cell. 2009;5:168–77.
pubmed: 19664991 doi: 10.1016/j.stem.2009.05.019
Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, et al. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell. 2010;6:25–36.
pubmed: 20085740 doi: 10.1016/j.stem.2009.11.013
Stamos JL, Weis WI. The beta-catenin destruction complex. Cold Spring Harb Perspect Biol. 2013;5:a007898.
pubmed: 23169527 pmcid: 3579403 doi: 10.1101/cshperspect.a007898
Polakis P. Wnt signaling in cancer. Cold Spring Harb Perspect Biol. 2012;4:a008052.
pubmed: 22438566 pmcid: 3331705 doi: 10.1101/cshperspect.a008052
Miyamoto Y, Yamauchi J, Sanbe A, Tanoue A. Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth. Exp Cell Res. 2007;313:791–804.
pubmed: 17196961 doi: 10.1016/j.yexcr.2006.11.017
Gadea G, Blangy A. Dock-family exchange factors in cell migration and disease. Eur J Cell Biol. 2014;93:466–77.
pubmed: 25022758 doi: 10.1016/j.ejcb.2014.06.003
Shi L. Dock protein family in brain development and neurological disease. Commun Integr Biol. 2013;6:e26839.
pubmed: 24563715 pmcid: 3922786 doi: 10.4161/cib.26839
Shaheen R, Faqeih E, Sunker A, Morsy H, Al-Sheddi T, Shamseldin HE, et al. Recessive mutations in DOCK6, encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and Adams-Oliver syndrome. Am J Hum Genet. 2011;89:328–33.
pubmed: 21820096 pmcid: 3155174 doi: 10.1016/j.ajhg.2011.07.009
Yamauchi J, Miyamoto Y, Chan JR, Tanoue A. ErbB2 directly activates the exchange factor Dock7 to promote Schwann cell migration. J Cell Biol. 2008;181:351–65.
pubmed: 18426980 pmcid: 2315680 doi: 10.1083/jcb.200709033
Gotoh K, Tanaka Y, Nishikimi A, Inayoshi A, Enjoji M, Takayanagi R, et al. Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells. Blood. 2008;111:2973–6.
pubmed: 18198348 doi: 10.1182/blood-2007-09-112169
McNiven MA, Baldassarre M, Buccione R. The role of dynamin in the assembly and function of podosomes and invadopodia. Front Biosci. 2004;9:1944–53.
pubmed: 14977600 doi: 10.2741/1348
Chen X, Leung SY, Yuen ST, Chu KM, Ji J, Li R, et al. Variation in gene expression patterns in human gastric cancers. Mol Biol Cell. 2003;14:3208–15.
pubmed: 12925757 pmcid: 181561 doi: 10.1091/mbc.e02-12-0833
Wang Q, Wen YG, Li DP, Xia J, Zhou CZ, Yan DW, et al. Upregulated INHBA expression is associated with poor survival in gastric cancer. Med Oncol. 2012;29:77–83.
pubmed: 21132402 doi: 10.1007/s12032-010-9766-y
Cho JY, Lim JY, Cheong JH, Park YY, Yoon SL, Kim SM, et al. Gene expression signature-based prognostic risk score in gastric cancer. Clin Cancer Res. 2011;17:1850–7.
pubmed: 21447720 pmcid: 3078023 doi: 10.1158/1078-0432.CCR-10-2180
Bravo-Cordero JJ, Hodgson L, Condeelis J. Directed cell invasion and migration during metastasis. Curr Opin Cell Biol. 2012;24:277–83.
pubmed: 22209238 doi: 10.1016/j.ceb.2011.12.004
Han ME, Jeon TY, Hwang SH, Lee YS, Kim HJ, Shim HE, et al. Cancer spheres from gastric cancer patients provide an ideal model system for cancer stem cell research. Cell Mol Life Sci. 2011;68:3589–605.
pubmed: 21448722 doi: 10.1007/s00018-011-0672-z
Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells–perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res. 2006;66:9339–44.
pubmed: 16990346 doi: 10.1158/0008-5472.CAN-06-3126
Lou H, Dean M. Targeted therapy for cancer stem cells: the patched pathway and ABC transporters. Oncogene. 2007;26:1357–60.
pubmed: 17322922 doi: 10.1038/sj.onc.1210200
D’Errico M, de Rinaldis E, Blasi MF, Viti V, Falchetti M, Calcagnile A, et al. Genome-wide expression profile of sporadic gastric cancers with microsatellite instability. Eur J Cancer. 2009;45:461–9.
pubmed: 19081245 doi: 10.1016/j.ejca.2008.10.032
Gilles C, Polette M, Mestdagt M, Nawrocki-Raby B, Ruggeri P, Birembaut P, et al. Transactivation of vimentin by beta-catenin in human breast cancer cells. Cancer Res. 2003;63:2658–64.
pubmed: 12750294
Saegusa M, Hashimura M, Kuwata T, Hamano M, Okayasu I. Upregulation of TCF4 expression as a transcriptional target of beta-catenin/p300 complexes during trans-differentiation of endometrial carcinoma cells. Lab Invest. 2005;85:768–79.
pubmed: 15806138 doi: 10.1038/labinvest.3700273
Notani D, Gottimukkala KP, Jayani RS, Limaye AS, Damle MV, Mehta S, et al. Global regulator SATB1 recruits beta-catenin and regulates T(H)2 differentiation in Wnt-dependent manner. PLoS Biol. 2010;8:e1000296.
pubmed: 20126258 pmcid: 2811152 doi: 10.1371/journal.pbio.1000296
Upadhyay G, Goessling W, North TE, Xavier R, Zon LI, Yajnik V. Molecular association between beta-catenin degradation complex and Rac guanine exchange factor DOCK4 is essential for Wnt/beta-catenin signaling. Oncogene. 2008;27:5845–55.
pubmed: 18641688 pmcid: 4774646 doi: 10.1038/onc.2008.202
Debruyne DN, Turchi L, Burel-Vandenbos F, Fareh M, Almairac F, Virolle V, et al. DOCK4 promotes loss of proliferation in glioblastoma progenitor cells through nuclear beta-catenin accumulation and subsequent miR-302-67 cluster expression. Oncogene. 2018;37:241–54.
pubmed: 28925399 doi: 10.1038/onc.2017.323
Jamieson C, Lui C, Brocardo MG, Martino-Echarri E, Henderson BR. Rac1 augments Wnt signaling by stimulating beta-catenin-lymphoid enhancer factor-1 complex assembly independent of beta-catenin nuclear import. J Cell Sci. 2015;128:3933–46.
pubmed: 26403202 pmcid: 4657330
Wu X, Tu X, Joeng KS, Hilton MJ, Williams DA, Long F. Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell. 2008;133:340–53.
pubmed: 18423204 pmcid: 2390926 doi: 10.1016/j.cell.2008.01.052
O’Dwyer D, Ralton LD, O’Shea A, Murray GI. The proteomics of colorectal cancer: identification of a protein signature associated with prognosis. PLoS ONE. 2011;6:e27718.
pubmed: 22125622 pmcid: 3220687 doi: 10.1371/journal.pone.0027718
Li X, Jiang M, Chen D, Xu B, Wang R, Chu Y, et al. miR-148b-3p inhibits gastric cancer metastasis by inhibiting the Dock6/Rac1/Cdc42 axis. J Exp Clin Cancer Res. 2018;37:71.
pubmed: 29587866 pmcid: 5872400 doi: 10.1186/s13046-018-0729-z
Al-Hajj M. Cancer stem cells and oncology therapeutics. Curr Opin Oncol. 2007;19:61–64.
pubmed: 17133114 doi: 10.1097/CCO.0b013e328011a8d6
Yoon CH, Hyun KH, Kim RK, Lee H, Lim EJ, Chung HY, et al. The small GTPase Rac1 is involved in the maintenance of stemness and malignancies in glioma stem-like cells. FEBS Lett. 2011;585:2331–8.
pubmed: 21704033 doi: 10.1016/j.febslet.2011.05.070
Mao J, Fan S, Ma W, Fan P, Wang B, Zhang J, et al. Roles of Wnt/beta-catenin signaling in the gastric cancer stem cells proliferation and salinomycin treatment. Cell Death Dis. 2014;5:e1039.
pubmed: 24481453 pmcid: 4040703 doi: 10.1038/cddis.2013.515
Chahdi A, Raufman JP. The Cdc42/Rac nucleotide exchange factor protein beta1Pix (Pak-interacting exchange factor) modulates beta-catenin transcriptional activity in colon cancer cells: evidence for direct interaction of beta1PIX with beta-catenin. J Biol Chem. 2013;288:34019–29.
pubmed: 24129564 pmcid: 3837141 doi: 10.1074/jbc.M113.480103
Buongiorno P, Pethe VV, Charames GS, Esufali S, Bapat B. Rac1 GTPase and the Rac1 exchange factor Tiam1 associate with Wnt-responsive promoters to enhance beta-catenin/TCF-dependent transcription in colorectal cancer cells. Mol Cancer. 2008;7:73.
pubmed: 18826597 pmcid: 2565678 doi: 10.1186/1476-4598-7-73
Schlessinger K, Hall A, Tolwinski N. Wnt signaling pathways meet Rho GTPases. Genes Dev. 2009;23:265–77.
pubmed: 19204114 doi: 10.1101/gad.1760809
Japanese Gastric Cancer A. Japanese classification of gastric carcinoma—2nd english edition. Gastric Cancer. 1998;1:10–24.
doi: 10.1007/PL00011681
Tsai CY, Chi HC, Chi LM, Yang HY, Tsai MM, Lee KF, et al. Argininosuccinate synthetase 1 contributes to gastric cancer invasion and progression by modulating autophagy. FASEB J. 2018;32:2601–14.
pubmed: 29401583 doi: 10.1096/fj.201700094r
Chi HC, Chen SL, Lin SL, Tsai CY, Chuang WY, Lin YH, et al. Thyroid hormone protects hepatocytes from HBx-induced carcinogenesis by enhancing mitochondrial turnover. Oncogene. 2017;36:5274–84.
pubmed: 28504722 doi: 10.1038/onc.2017.136
Chi HC, Chen SL, Tsai CY, Chuang WY, Huang YH, Tsai MM, et al. Thyroid hormone suppresses hepatocarcinogenesis via DAPK2 and SQSTM1-dependent selective autophagy. Autophagy. 2016;12:2271–85.
pubmed: 27653365 pmcid: 5173272 doi: 10.1080/15548627.2016.1230583
Vojnits K, Pan H, Mu X, Li Y. Characterization of an injury induced population of muscle-derived stem cell-like cells. Sci Rep. 2015;5:17355.
pubmed: 26611864 pmcid: 4661568 doi: 10.1038/srep17355
Chen G, Deng X. Cell synchronization by double thymidine block. Bio Protoc. 2018;8:e2994.
pubmed: 30263905 pmcid: 6156087
Chi HC, Chen SL, Cheng YH, Lin TK, Tsai CY, Tsai MM, et al. Chemotherapy resistance and metastasis-promoting effects of thyroid hormone in hepatocarcinoma cells are mediated by suppression of FoxO1 and Bim pathway. Cell Death Dis. 2016;7:e2324.
pubmed: 27490929 pmcid: 5108316 doi: 10.1038/cddis.2016.227

Auteurs

Hsiang-Cheng Chi (HC)

Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
ORCID: 0000-0001-5691-2453

Chung-Ying Tsai (CY)

Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Chia-Siu Wang (CS)

Department of General Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
ORCID: 0000-0002-9357-2571

Huang-Yu Yang (HY)

Kidney Research Institute, Nephrology Department, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Graduate Institute of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Chien-Hui Lo (CH)

Institute of Biochemistry and Molecular Biology, College of Life Science, National Yang-Ming University, Taipei, Taiwan.
Taiwan International Graduate Program (TIGP) in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.

Won-Jing Wang (WJ)

Institute of Biochemistry and Molecular Biology, College of Life Science, National Yang-Ming University, Taipei, Taiwan.
Taiwan International Graduate Program (TIGP) in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.

Kam-Fai Lee (KF)

Department of Pathology, Chang Gung Memorial Hospital, Chiayi, Taiwan.

Li-Yin Lai (LY)

Department of Microbiology and Internal Medicine, National Taiwan University, Taipei, Taiwan.
ORCID: 0000-0003-0244-6834

Ji-Hong Hong (JH)

Department of Radiation Oncology, Institute for Radiological Research, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.

Yen-Fang Chang (YF)

Graduate Institute of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.

Ming-Ming Tsai (MM)

Department of General Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.

Chau-Ting Yeh (CT)

Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.

Cheng Heng Wu (CH)

Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.

Ching-Chuan Hsieh (CC)

Department of General Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.

Lu-Hai Wang (LH)

Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. lu-hai.wang@nhri.org.tw.
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Miaoli County, Taiwan. lu-hai.wang@nhri.org.tw.

Wei-Jan Chen (WJ)

Division of Cardiology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. wjchen@adm.cgmh.org.tw.
ORCID: 0000-0001-8088-5475

Kwang-Huei Lin (KH)

Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan. khlin@mail.cgu.edu.tw.
Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan. khlin@mail.cgu.edu.tw.
Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. khlin@mail.cgu.edu.tw.
ORCID: 0000-0002-5649-2222

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Phénomènes physiologiques › Mouvement cellulaire › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Régulateurs des protéines G › Facteurs d'échange de nucléotides guanyliques › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Régions du corps › Transplants › Hétérogreffes › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Immunohistochimie › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Tests immunologiques › Immunophénotypage › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Cellules › Cellules souches › Cellules souches tumorales › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Phénomènes physiologiques › Radiotolérance › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies gastro-intestinales › Maladies de l'estomac › Tumeurs de l'estomac › DOCK6 promotes chemo- and radioresistance of...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Wnt › DOCK6 promotes chemo- and radioresistance of...