FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome.

Animals Carcinogenesis / metabolism Cell Proliferation Cellular Senescence Female Fructose-Bisphosphatase / physiology Gene Expression Regulation, Neoplastic Hepatic Stellate Cells / metabolism Humans Liver Neoplasms / metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Tumor Microenvironment Xenograft Model Antitumor Assays

Journal

Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575

Informations de publication

Date de publication:
06 2020
Historique:
received: 30 07 2019
accepted: 26 03 2020
pubmed: 6 5 2020
medline: 17 9 2020
entrez: 6 5 2020
Statut: ppublish

Résumé

The crosstalk between deregulated hepatocyte metabolism and cells within the tumour microenvironment, as well as the consequent effects on liver tumorigenesis, are not completely understood. We show here that hepatocyte-specific loss of the gluconeogenic enzyme fructose 1,6-bisphosphatase 1 (FBP1) disrupts liver metabolic homeostasis and promotes tumour progression. FBP1 is universally silenced in both human and murine liver tumours. Hepatocyte-specific Fbp1 deletion results in steatosis, concomitant with activation and senescence of hepatic stellate cells (HSCs), exhibiting a senescence-associated secretory phenotype. Depleting senescent HSCs by 'senolytic' treatment with dasatinib/quercetin or ABT-263 inhibits tumour progression. We further demonstrate that FBP1-deficient hepatocytes promote HSC activation by releasing HMGB1; blocking its release with the small molecule inflachromene limits FBP1-dependent HSC activation, the subsequent development of the senescence-associated secretory phenotype and tumour progression. Collectively, these findings provide genetic evidence for FBP1 as a metabolic tumour suppressor in liver cancer and establish a critical crosstalk between hepatocyte metabolism and HSC senescence that promotes tumour growth.

Identifiants

DOI: 10.1038/s41556-020-0511-2 PMID: 32367049 PMC: PMC7286794
pubmed: 32367049
doi: 10.1038/s41556-020-0511-2
pii: 10.1038/s41556-020-0511-2
pmc: PMC7286794
mid: NIHMS1579974
doi:

Substances chimiques

Fructose-Bisphosphatase EC 3.1.3.11

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

728-739

Subventions

Organisme : NCI NIH HHS
ID : R35 CA220483
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007229
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA104838
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016520
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA221838
Pays : United States

Commentaires et corrections

Type : CommentIn

Références

Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2017. CA Cancer J. Clin. 67, 7–30 (2017).
pubmed: 28055103 doi: 10.3322/caac.21387
The Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell 169, 1327–1341 (2017).
Greten, T. F., Wang, X. W. & Korangy, F. Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches. Gut 64, 842–848 (2015).
pubmed: 25666193 pmcid: 6311419 doi: 10.1136/gutjnl-2014-307990
Ringelhan, M., Pfister, D., O’Connor, T., Pikarsky, E. & Heikenwalder, M. The immunology of hepatocellular carcinoma. Nat. Immunol. 19, 222–232 (2018).
pubmed: 29379119 doi: 10.1038/s41590-018-0044-z
Friedman, S. L. Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol. Rev. 88, 125–172 (2008).
pubmed: 18195085 pmcid: 2888531 doi: 10.1152/physrev.00013.2007
Affo, S., Yu, L. X. & Schwabe, R. F. The role of cancer-associated fibroblasts and fibrosis in liver cancer. Annu. Rev. Pathol. 12, 153–186 (2017).
pubmed: 27959632 doi: 10.1146/annurev-pathol-052016-100322
Gomes, A. L. et al. Metabolic inflammation-associated Il-17A causes non-alcoholic steatohepatitis and hepatocellular carcinoma. Cancer Cell 30, 161–175 (2016).
pubmed: 27411590 doi: 10.1016/j.ccell.2016.05.020
Ma, C. et al. NAFLD causes selective CD4
pubmed: 26934227 pmcid: 4786464 doi: 10.1038/nature16969
Shalapour, S. et al. Inflammation-induced IgA
pubmed: 29144460 pmcid: 5884449 doi: 10.1038/nature24302
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M. & Sanyal, A. J. Mechanisms of NAFLD development and therapeutic strategies. Nat. Med. 24, 908–922 (2018).
pubmed: 29967350 pmcid: 6553468 doi: 10.1038/s41591-018-0104-9
Arab, J. P., Arrese, M. & Trauner, M. Recent insights into the pathogenesis of nonalcoholic fatty liver disease. Annu. Rev. Pathol. 13, 321–350 (2018).
pubmed: 29414249 doi: 10.1146/annurev-pathol-020117-043617
Michelotti, G. A., Machado, M. V. & Diehl, A. M. NAFLD, NASH and liver cancer. Nat. Rev. Gastroenterol. Hepatol. 10, 656–665 (2013).
pubmed: 24080776 doi: 10.1038/nrgastro.2013.183
Dong, C. et al. Loss of FBP1 by Snail-mediated repression provides metabolic advantages in basal-like breast cancer. Cancer Cell 23, 316–331 (2013).
pubmed: 23453623 pmcid: 3703516 doi: 10.1016/j.ccr.2013.01.022
Hirata, H. et al. Decreased expression of fructose-1,6-bisphosphatase associates with glucose metabolism and tumor progression in hepatocellular carcinoma. Cancer Res. 76, 3265–3276 (2016).
pubmed: 27197151 doi: 10.1158/0008-5472.CAN-15-2601
Li, B. et al. Fructose-1,6-bisphosphatase opposes renal carcinoma progression. Nature 513, 251–255 (2014).
pubmed: 25043030 pmcid: 4162811 doi: 10.1038/nature13557
Gebhardt, R. Metabolic zonation of the liver: regulation and implications for liver function. Pharmacol. Ther. 53, 275–354 (1992).
pubmed: 1409850 doi: 10.1016/0163-7258(92)90055-5
Katz, S. F. et al. Disruption of Trp53 in livers of mice induces formation of carcinomas with bilineal differentiation. Gastroenterology 142, 1229–1239 (2012).
pubmed: 22342966 doi: 10.1053/j.gastro.2012.02.009
Tschaharganeh, D. F. et al. p53-dependent Nestin regulation links tumor suppression to cellular plasticity in liver cancer. Cell 158, 579–592 (2014).
pubmed: 25083869 pmcid: 4221237 doi: 10.1016/j.cell.2014.05.051
Asgharpour, A. et al. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. J. Hepatol. 65, 579–588 (2016).
pubmed: 27261415 pmcid: 5012902 doi: 10.1016/j.jhep.2016.05.005
Tsuchida, T. et al. A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer. J. Hepatol. 69, 385–395 (2018).
pubmed: 29572095 pmcid: 6054570 doi: 10.1016/j.jhep.2018.03.011
Arruda, A. P. et al. Chronic enrichment of hepatic endoplasmic reticulum–mitochondria contact leads to mitochondrial dysfunction in obesity. Nat. Med. 20, 1427–1435 (2014).
pubmed: 25419710 pmcid: 4412031 doi: 10.1038/nm.3735
Febbraio, M. A. et al. Preclinical models for studying NASH-driven HCC: how useful are they? Cell Metab. 29, 18–26 (2019).
pubmed: 30449681 doi: 10.1016/j.cmet.2018.10.012
Nakagawa, H. et al. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell 26, 331–343 (2014).
pubmed: 25132496 pmcid: 4165611 doi: 10.1016/j.ccr.2014.07.001
Bakiri, L. & Wagner, E. F. Mouse models for liver cancer. Mol. Oncol. 7, 206–223 (2013).
pubmed: 23428636 pmcid: 5528415 doi: 10.1016/j.molonc.2013.01.005
He, G. et al. Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell 155, 384–396 (2013).
pubmed: 24120137 pmcid: 4015514 doi: 10.1016/j.cell.2013.09.031
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
Yoshimoto, S. et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499, 97–101 (2013).
pubmed: 23803760 doi: 10.1038/nature12347
Schnabl, B., Purbeck, C. A., Choi, Y. H., Hagedorn, C. H. & Brenner, D. Replicative senescence of activated human hepatic stellate cells is accompanied by a pronounced inflammatory but less fibrogenic phenotype. Hepatology 37, 653–664 (2003).
pubmed: 12601363 doi: 10.1053/jhep.2003.50097
Henderson, N. C. et al. Targeting of α
pubmed: 24216753 doi: 10.1038/nm.3282
Baar, M. P. et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging. Cell 169, 132–147 (2017).
pubmed: 28340339 pmcid: 5556182 doi: 10.1016/j.cell.2017.02.031
Coppe, J. P., Desprez, P. Y., Krtolica, A. & Campisi, J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 5, 99–118 (2010).
pubmed: 20078217 pmcid: 4166495 doi: 10.1146/annurev-pathol-121808-102144
Zhu, Y. et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14, 644–658 (2015).
pubmed: 25754370 pmcid: 4531078 doi: 10.1111/acel.12344
Farr, J. N. et al. Targeting cellular senescence prevents age-related bone loss in mice. Nat. Med. 23, 1072–1079 (2017).
pubmed: 28825716 pmcid: 5657592 doi: 10.1038/nm.4385
Ogrodnik, M. et al. Cellular senescence drives age-dependent hepatic steatosis. Nat. Commun. 8, 15691 (2017).
pubmed: 28608850 pmcid: 5474745 doi: 10.1038/ncomms15691
Xu, M. et al. Senolytics improve physical function and increase lifespan in old age. Nat. Med. 24, 1246–1256 (2018).
pubmed: 29988130 pmcid: 6082705 doi: 10.1038/s41591-018-0092-9
Zhu, Y. et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell 15, 428–435 (2016).
pubmed: 26711051 pmcid: 4854923 doi: 10.1111/acel.12445
Chang, J. et al. Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nat. Med. 22, 78–83 (2016).
pubmed: 26657143 doi: 10.1038/nm.4010
Guieze, R. et al. Mitochondrial reprogramming underlies resistance to BCL-2 inhibition in lymphoid malignancies. Cancer Cell 36, 369–384 (2019).
pubmed: 31543463 doi: 10.1016/j.ccell.2019.08.005
Hernandez, C. et al. HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis. J. Clin. Invest. 128, 2436–2451 (2018).
pubmed: 29558367 pmcid: 5983315 doi: 10.1172/JCI91786
Khambu, B. et al. HMGB1 promotes ductular reaction and tumorigenesis in autophagy-deficient livers. J. Clin. Invest. 128, 2419–2435 (2018).
pubmed: 29558368 pmcid: 5983330 doi: 10.1172/JCI91814
Ge, X. et al. High mobility group box-1 drives fibrosis progression signaling via the receptor for advanced glycation end products in mice. Hepatology 68, 2380–2404 (2018).
pubmed: 29774570 pmcid: 6240507 doi: 10.1002/hep.30093
Chen, R. et al. Emerging role of high-mobility group box 1 (HMGB1) in liver diseases. Mol. Med. 19, 357–366 (2013).
pubmed: 24306421 pmcid: 3883963 doi: 10.2119/molmed.2013.00099
Kim, K. H., Chen, C. C., Monzon, R. I. & Lau, L. F. Matricellular protein CCN1 promotes regression of liver fibrosis through induction of cellular senescence in hepatic myofibroblasts. Mol. Cell. Biol. 33, 2078–2090 (2013).
pubmed: 23508104 pmcid: 3647960 doi: 10.1128/MCB.00049-13
Seki, E. et al. CCR2 promotes hepatic fibrosis in mice. Hepatology 50, 185–197 (2009).
pubmed: 19441102 pmcid: 2705470 doi: 10.1002/hep.22952
Lee, S. et al. A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation. Nat. Chem. Biol. 10, 1055–1060 (2014).
pubmed: 25306442 doi: 10.1038/nchembio.1669
Huangyang, P. et al. Fructose-1,6-bisphosphatase 2 inhibits sarcoma progression by restraining mitochondrial biogenesis. Cell Metab. 31, 174–188 (2019).
Lee, S. & Schmitt, C. A. The dynamic nature of senescence in cancer. Nat. Cell Biol. 21, 94–101 (2019).
pubmed: 30602768 doi: 10.1038/s41556-018-0249-2
Eggert, T. et al. Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression. Cancer Cell 30, 533–547 (2016).
pubmed: 27728804 doi: 10.1016/j.ccell.2016.09.003
Kang, T. W. et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479, 547–551 (2011).
pubmed: 22080947 doi: 10.1038/nature10599
Gorgoulis, V. et al. Cellular senescence: defining a path forward. Cell 179, 813–827 (2019).
pubmed: 31675495 doi: 10.1016/j.cell.2019.10.005
Lujambio, A. et al. Non-cell-autonomous tumor suppression by p53. Cell 153, 449–460 (2013).
pubmed: 23562644 pmcid: 3702034 doi: 10.1016/j.cell.2013.03.020
Liu, F. et al. Ceramide activates lysosomal cathepsin B and cathepsin D to attenuate autophagy and induces ER stress to suppress myeloid-derived suppressor cells. Oncotarget 7, 83907–83925 (2016).
pubmed: 27880732 pmcid: 5356634 doi: 10.18632/oncotarget.13438
Tian, Z., Chen, Y. & Gao, B. Natural killer cells in liver disease. Hepatology 57, 1654–1662 (2013).
pubmed: 23111952 pmcid: 3573257 doi: 10.1002/hep.26115
Baker, D. J. et al. Clearance of p16
pubmed: 22048312 pmcid: 3468323 doi: 10.1038/nature10600
Baker, D. J. et al. Naturally occurring p16
pubmed: 26840489 pmcid: 4845101 doi: 10.1038/nature16932
Kirkland, J. L. & Tchkonia, T. Cellular senescence: a translational perspective. EBioMedicine 21, 21–28 (2017).
pubmed: 28416161 pmcid: 5514381 doi: 10.1016/j.ebiom.2017.04.013
Kirkland, J. L., Tchkonia, T., Zhu, Y., Niedernhofer, L. J. & Robbins, P. D. The clinical potential of senolytic drugs. J. Am. Geriatr. Soc. 65, 2297–2301 (2017).
pubmed: 28869295 pmcid: 5641223 doi: 10.1111/jgs.14969
Childs, B. G. et al. Senescent cells: an emerging target for diseases of ageing. Nat. Rev. Drug Discov. 16, 718–735 (2017).
pubmed: 28729727 pmcid: 5942225 doi: 10.1038/nrd.2017.116
Dorr, J. R. et al. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature 501, 421–425 (2013).
pubmed: 23945590 doi: 10.1038/nature12437
Toso, A. et al. Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Rep. 9, 75–89 (2014).
doi: 10.1016/j.celrep.2014.08.044 pubmed: 25263564
Demaria, M. et al. Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov. 7, 165–176 (2017).
pubmed: 27979832 doi: 10.1158/2159-8290.CD-16-0241
Wang, C. et al. Inducing and exploiting vulnerabilities for the treatment of liver cancer. Nature 574, 268–272 (2019).
pubmed: 31578521 pmcid: 6858884 doi: 10.1038/s41586-019-1607-3
Mu, X. et al. Hepatocellular carcinoma originates from hepatocytes and not from the progenitor/biliary compartment. J. Clin. Invest. 125, 3891–3903 (2015).
pubmed: 26348897 pmcid: 4607132 doi: 10.1172/JCI77995
Mederacke, I., Dapito, D. H., Affo, S., Uchinami, H. & Schwabe, R. F. High-yield and high-purity isolation of hepatic stellate cells from normal and fibrotic mouse livers. Nat. Protoc. 10, 305–315 (2015).
pubmed: 25612230 pmcid: 4681437 doi: 10.1038/nprot.2015.017
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16
pubmed: 9054499 doi: 10.1016/S0092-8674(00)81902-9
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).
doi: 10.1073/pnas.0506580102
Riscal, R. et al. Chromatin-bound MDM2 regulates serine metabolism and redox homeostasis independently of p53. Mol. Cell 62, 890–902 (2016).
pubmed: 27264869 doi: 10.1016/j.molcel.2016.04.033
Possemato, R. et al. Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature 476, 346–350 (2011).
pubmed: 21760589 pmcid: 21760589 doi: 10.1038/nature10350

Auteurs

Fuming Li (F)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Peiwei Huangyang (P)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Helen Diller Cancer Center, UCSF, San Francisco, CA, USA.

Michelle Burrows (M)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Kathy Guo (K)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kornberg School of Dentistry, Temple University, Philadelphia, PA, USA.

Romain Riscal (R)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
ORCID: 0000-0001-8969-224X

Jason Godfrey (J)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
ORCID: 0000-0002-8195-8602

Kyoung Eun Lee (KE)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.

Nan Lin (N)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Trinity Partners, LLC, Waltham, MA, USA.

Pearl Lee (P)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
ORCID: 0000-0002-1274-2891

Ian A Blair (IA)

Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
ORCID: 0000-0003-0366-8658

Brian Keith (B)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
The Wistar Institute, Philadelphia, PA, USA.

Bo Li (B)

Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China. libo47@mail.sysu.edu.cn.
RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. libo47@mail.sysu.edu.cn.
ORCID: 0000-0002-7979-8339

M Celeste Simon (MC)

Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. celeste2@pennmedicine.upenn.edu.
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA, USA. celeste2@pennmedicine.upenn.edu.
ORCID: 0000-0001-9106-447X

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 › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Vieillissement › Vieillissement de la cellule › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Phosphoric monoester hydrolases › Fructose-1,6-diphosphatase › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Cellules › Cellules étoilées du foie › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Tumeurs du foie › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › FBP1 loss disrupts liver metabolism and...
questionsmedicales.fr › Techniques d'investigation › Transplantation tumorale › Tests d'activité antitumorale sur modèle de xénogreffe › FBP1 loss disrupts liver metabolism and...