Cited by 585Metabolism, Diabetes, and CancerCancer, Hypoxia, and MetabolismLung Cancer Treatments and Mutations

The DOI matches its Crossref record; 52 of the 53 references it cites were found in a registry or an index.

LKB1 Inactivation Dictates Therapeutic Response of Non-Small Cell Lung Cancer to the Metabolism Drug Phenformin

Open access

Shackelford, David B., Abt, Evan, Gerken, Laurie, Vasquez, Debbie S., Seki, Atsuko, Leblanc, Mathias, Wei, Liu, Fishbein, Michael C., Czernin, Johannes, Mischel, Paul S., Shaw, Reuben J.·2013·Cancer Cell

DOI 10.1016/j.ccr.2012.12.008PMC PMC3579627

Open this paper in CoChat — free account Open PDF

Abstract

The LKB1 (also called STK11) tumor suppressor is mutationally inactivated in ∼20% of non-small cell lung cancers (NSCLC). LKB1 is the major upstream kinase activating the energy-sensing kinase AMPK, making LKB1-deficient cells unable to appropriately sense metabolic stress. We tested the therapeutic potential of metabolic drugs in NSCLC and identified phenformin, a mitochondrial inhibitor and analog of the diabetes therapeutic metformin, as selectively inducing apoptosis in LKB1-deficient NSCLC cells. Therapeutic trials in Kras-dependent mouse models of NSCLC revealed that tumors with Kras and Lkb1 mutations, but not those with Kras and p53 mutations, showed selective response to phenformin as a single agent, resulting in prolonged survival. This study suggests phenformin as a cancer metabolism-based therapeutic to selectively target LKB1-deficient tumors.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1016/j.ccr.2012.12.008

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
AMPK Phosphorylation of Raptor Mediates a Metabolic Checkpoint
Gwinn, D. M., Shackelford, D. B., Egan, D. F., Mihaylova, M. M., Mery, A., Vasquez, D. S., Turk, B. E., & Shaw, R. J. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.003 · Cited by 3,849
Self-citation
Somatic mutations affect key pathways in lung adenocarcinoma
Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., Sougnez, C., Greulich, H., Muzny, D. M., Morgan, M. B., et al. (2008) · Nature · doi:10.1038/nature07423 · Cited by 2,681
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600
Self-citation
Metformin and reduced risk of cancer in diabetic patients
Evans, J. M. M., Donnelly, L. A., Emslie-Smith, A. M., Alessi, D. R., & Morris, A. D. (2005) · BMJ · doi:10.1136/bmj.38415.708634.f7 · Cited by 2,388
Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950
Self-citation
The LKB1-AMPK pathway: metabolism and growth control in tumour suppression
Shackelford, D. B., & Shaw, R. J. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2676 · Cited by 1,943
Self-citation
The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797
Self-citation

Flagged first, then by citations

Show all 53 references

1 of the 53 references couldn’t be matched to a known paper.

Sorted by citations

Items 201–300 of 585

Exploiting metabolic vulnerabilities of Non small cell lung carcinoma
Majem, B., Nadal, E., & Muñoz‐Pinedo, C. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.06.004 · Cited by 57
A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress
Ritho, J., Arold, S. T., & Yeh, E. T. H. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.07.002 · Cited by 53
Essential Role for Oxidative Phosphorylation in Cancer Progression
Maiuri, M. C., & Kroemer, G. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2014.12.013 · Cited by 56
Phenformin Inhibits Hedgehog-Dependent Tumor Growth through a Complex I-Independent Redox/Corepressor Module
Magno, L. D., Manni, S., Pastena, F. D., Coni, S., Macone, A., Cairoli, S., Sambucci, M., Infante, P., Moretti, M., Petroni, M., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.01.024 · Cited by 56
DeepLRHE: A Deep Convolutional Neural Network Framework to Evaluate the Risk of Lung Cancer Recurrence and Metastasis From Histopathology Images
Wu, Z., Wang, L., Li, C., Cai, Y., Liang, Y., Mo, X., Lu, Q., Dong, L., & Liu, Y. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00768 · Cited by 54
Cyclic fasting-mimicking diet in cancer treatment: Preclinical and clinical evidence
Vernieri, C., Ligorio, F., Tripathy, D., & Longo, V. D. (2024) · Cell Metabolism · doi:10.1016/j.cmet.2024.06.014 · Cited by 57
Computable cause‐and‐effect models of healthy and Alzheimer's disease states and their mechanistic differential analysis
Kodamullil, A. T., Younesi, E., Naz, M., Bagewadi, S., & Hofmann‐Apitius, M. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.02.006 · Cited by 52
Metformin enhances the response to radiotherapy in diabetic patients with rectal cancer
Oh, B. Y., Park, Y. A., Huh, J. W., Cho, Y. B., Yun, S. H., Lee, W. Y., Park, H. C., Choi, D. H., Park, Y. S., & Kim, H. C. (2016) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-016-2148-x · Cited by 52
Molecular Pathways: Preclinical Models and Clinical Trials with Metformin in Breast Cancer
Thompson, A. M. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0354 · Cited by 50
KRAS mutant lung cancer: progress thus far on an elusive therapeutic target
Bhattacharya, S., Socinski, M. A., & Burns, T. F. (2015) · Clinical and Translational Medicine · doi:10.1186/s40169-015-0075-0 · Cited by 53
WEE1 Kinase Inhibitor AZD1775 Has Preclinical Efficacy in LKB1-Deficient Non–Small Cell Lung Cancer
Richer, A. L., Cala, J. M., O’Brien, K., Carson, V. M., Inge, L. J., & Whitsett, T. G. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-3565 · Cited by 51
Aurora-A-mediated phosphorylation of LKB1 compromises LKB1/AMPK signaling axis to facilitate NSCLC growth and migration
Zheng, X., Chi, J., Zhi, J., Zhang, H., Yue, D., Zhao, J., Li, D., Li, Y., Gao, M., & Guo, J. (2017) · Oncogene · doi:10.1038/onc.2017.354 · Cited by 51
Targeting Cell Metabolism as Cancer Therapy
Ngoi, N. Y. L., Eu, J. Q., Hirpara, J. L., Wang, L., Lim, J. S. J., Lee, S. C., Lim, Y., Pervaiz, S., Goh, B. C., & Wong, A. L. A. (2019) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7947 · Cited by 52
Altered Mitochondria Functionality Defines a Metastatic Cell State in Lung Cancer and Creates an Exploitable Vulnerability
Chuang, C.-H., Dorsch, M., Dujardin, P., Silas, S., Ueffing, K., Hölken, J. M., Yang, D., Winslow, M. M., & Grüner, B. M. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-1865 · Cited by 55
LKB1 Represses Focal Adhesion Kinase (FAK) Signaling via a FAK-LKB1 Complex to Regulate FAK Site Maturation and Directional Persistence
Kline, E. R., Shupe, J. A., Gilbert‐Ross, M., Zhou, W., & Marcus, A. I. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.444620 · Cited by 48
Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell Mitochondria
Guo, Z., Sevrioukova, I. F., Denisov, I. G., Zhang, X., Chiu, T.-L., Thomas, D. G., Hanse, E. A., Cuellar, R. A. D., Grinkova, Y. V., Langenfeld, V. W., et al. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.08.009 · Cited by 54
Contributions of AMPK and p53 dependent signaling to radiation response in the presence of metformin
Muaddi, H., Chowdhury, S., Vellanki, R. N., Zamiara, P., & Koritzinsky, M. (2013) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2013.06.014 · Cited by 51
LKB1 tumor suppressor: Therapeutic opportunities knock when LKB1 is inactivated
Zhou, W., Zhang, J., & Marcus, A. I. (2014) · Genes & Diseases · doi:10.1016/j.gendis.2014.06.002 · Cited by 48
LKB1 is a central regulator of tumor initiation and pro-growth metabolism in ErbB2-mediated breast cancer
Dupuy, F., Griss, T., Blagih, J., Bridon, G., Avizonis, D. Z., Ling, C., Dong, Z., Siwak, D. R., Annis, M. G., Mills, G. B., et al. (2013) · Cancer & Metabolism · doi:10.1186/2049-3002-1-18 · Cited by 53
Regulation of organelle function by metformin
Kim, J., & You, Y. (2017) · IUBMB Life · doi:10.1002/iub.1633 · Cited by 50
Dysregulation of mRNA translation and energy metabolism in cancer
Leibovitch, M., & Topisirović, I. (2017) · Advances in Biological Regulation · doi:10.1016/j.jbior.2017.11.001 · Cited by 46
Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR
Veiga, S. R., Ge, X., Mercer, C. A., Hernández‐Álvarez, M. I., Thomas, H. E., Hernández‐Losa, J., y Cajal, S. R., Antonio Zorzano, A., Thomas, G., & Kozma, S. C. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-0177 · Cited by 49
Randomized Phase 0/I Trial of the Mitochondrial Inhibitor ME-344 or Placebo Added to Bevacizumab in Early HER2-Negative Breast Cancer
Quintela-Fandiño, M., Morales, S. M., Cortés-Salgado, A., Manso, L., Apala, J. V., Muñoz, M., Cudós, A. G., Fortuny, J. S., Gión, M., López‐Alonso, A., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2023 · Cited by 50
Metabolic Regulation of Epigenetic Modifications and Cell Differentiation in Cancer
Saggese, P., Sellitto, A., Martinez, C. A., Giurato, G., Nassa, G., Rizzo, F. M., Tarallo, R., & Scafoglio, C. (2020) · Cancers · doi:10.3390/cancers12123788 · Cited by 46
Metabolic targeting of cancer by a ubiquinone uncompetitive inhibitor of mitochondrial complex I
Jain, S., Hu, C., Kluza, J., Ke, W., Tian, G., Giurgiu, M., Bleilevens, A., Campos, A. R., Charbono, A., Stickeler, E., et al. (2021) · Cell chemical biology · doi:10.1016/j.chembiol.2021.11.002 · Cited by 48
Inhibition of oxidative phosphorylation suppresses the development of osimertinib resistance in a preclinical model of EGFR-driven lung adenocarcinoma
Martin, M. J., Eberlein, C., Taylor, M. A., Ashton, S. E., Robinson, D. M., & Cross, D. A. E. (2016) · Oncotarget · doi:10.18632/oncotarget.13388 · Cited by 52
Metformin Has Positive Therapeutic Effects in Colon Cancer and Lung Cancer
Henderson, D., Frieson, D., Zuber, J. K., & Solomon, S. S. (2017) · The American Journal of the Medical Sciences · doi:10.1016/j.amjms.2017.05.006 · Cited by 48
Long noncoding RNA H19 participates in metformin‐mediated inhibition of gastric cancer cell invasion
Li, P., Tong, L., Song, Y., Sun, J., Shi, J., Wu, Z., Diao, Y., Li, Y., & Wang, Z. (2018) · Journal of Cellular Physiology · doi:10.1002/jcp.27269 · Cited by 48
The CREB coactivator CRTC2 promotes oncogenesis in LKB1-mutant non–small cell lung cancer
Rodón, L., Svensson, R. U., Wiater, E., Chun, M. G. H., Tsai, W., Eichner, L. J., Shaw, R. J., & Montminy, M. (2019) · Science Advances · doi:10.1126/sciadv.aaw6455 · Cited by 50
Self-citation
An Asp to Strike Out Cancer? Therapeutic Possibilities Arising from Aspartate’s Emerging Roles in Cell Proliferation and Survival
Helenius, I. T., Madala, H. R., & Yeh, J.-R. J. (2021) · Biomolecules · doi:10.3390/biom11111666 · Cited by 43
LKB1 controls inflammatory potential through CRTC2-dependent histone acetylation
Compton, S. E., Kitchen-Goosen, S. M., DeCamp, L. M., Lau, K. H., Mabvakure, B. M., Vos, M., Williams, K. S., Wong, K., Shi, X., Rothbart, S. B., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.04.017 · Cited by 48
Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells
Teixeira, S. F., Guimarães, I. D. S., Madeira, K. P., Daltoé, R. D., Silva, I. V., & Rangel, L. B. A. (2013) · Jornal Brasileiro de Pneumologia · doi:10.1590/s1806-37132013000600002 · Cited by 47
Quantitative In Vivo Proteomics of Metformin Response in Liver Reveals AMPK-Dependent and -Independent Signaling Networks
Stein, B. D., Calzolari, D., Hellberg, K., Hu, Y., He, L., Hung, C., Toyama, E. Q., Ross, D. S., Lillemeier, B. F., Cantley, L. C., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.10.117 · Cited by 44
Self-citation
Heightening Energetic Stress Selectively Targets LKB1-Deficient Non–Small Cell Lung Cancers
Momcilovic, M., McMickle, R., Abt, E., Seki, A., Simko, S. A., Magyar, C., Stout, D. B., Fishbein, M. C., Walser, T. C., Dubinett, S. M., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-0797 · Cited by 46
“Phenformin and MLN0128 combination therapy compound energy stress and induce apoptosis in LKB1-mutantNSCLC cells In a previous study, we identified the mTORC1 substrate phospho-4E-BP1 (P-4E-BP1) remained highly upregulated in KrasG12D;Lkb1 / ;Luc (KLluc) mouse lung tumors following phenformin treatment (7).”
InfluentialSelf-citation
Cancer genome and tumor microenvironment: Reciprocal crosstalk shapes lung cancer plasticity
Mansouri, S., Heylmann, D., Stiewe, T., Kracht, M., & Savai, R. (2022) · eLife · doi:10.7554/elife.79895 · Cited by 45
Metabolic advantages and vulnerabilities in brain metastases
Ciminera, A. K., Jandial, R., & Termini, J. S. (2017) · Clinical & Experimental Metastasis · doi:10.1007/s10585-017-9864-8 · Cited by 46
Metformin for non-small cell lung cancer patients: Opportunities and pitfalls
Lévy, A., & Doyen, J. (2018) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2018.03.001 · Cited by 46
Metabolic Pathways, Enzymes, and Metabolites: Opportunities in Cancer Therapy
Kumar, R., Mishra, A., Gautam, P., Feroz, Z., Vijayaraghavalu, S., Likos, E., Shukla, G. C., & Kumar, M. (2022) · Cancers · doi:10.3390/cancers14215268 · Cited by 50
LKB1-Dependent Regulation of TPI1 Creates a Divergent Metabolic Liability between Human and Mouse Lung Adenocarcinoma
Stein, B. D., Ferrarone, J. R., Gardner, E. E., Chang, J. W., Wu, D., Hollstein, P. E., Liang, R. J., Yuan, M., Chen, Q., Coukos, J. S., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0805 · Cited by 45
Self-citation
Metformin Use and Lung Cancer Risk in Patients with Diabetes
Sakoda, L. C., Ferrara, A. M., Achacoso, N. S., Peng, T., Ehrlich, S. F., Quesenberry, C. P., & Habel, L. A. (2015) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-14-0291 · Cited by 44
Targeting metabolism and AMP-activated kinase with metformin to sensitize non-small cell lung cancer (NSCLC) to cytotoxic therapy: translational biology and rationale for current clinical trials
Troncone, M. J., Cargnelli, S., Villani, L. A., Isfahanian, N., Broadfield, L. A., Zychla, L., Wright, J., Pond, G. R., Steinberg, G. R., & Tsakiridis, T. K. (2017) · Oncotarget · doi:10.18632/oncotarget.17496 · Cited by 45
Antidiabetic Biguanides Radiosensitize Hypoxic Colorectal Cancer Cells Through a Decrease in Oxygen Consumption
de Mey, S., Jiang, H., Corbet, C., Wang, H., Dufait, I., Ka, L. L., Bastien, E., Verovski, V. N., Gevaert, T., Féron, O., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01073 · Cited by 45
Metformin inhibits human non-small cell lung cancer by regulating AMPK–CEBPB–PDL1 signaling pathway
Lu, T., Li, M., Zhao, M., Huang, Y., Bi, G., Liang, J., Chen, Z., Zheng, Y., Xi, J., Lin, Z., et al. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-021-03116-x · Cited by 44
Role of LKB1-CRTC1 on Glycosylated COX-2 and Response to COX-2 Inhibition in Lung Cancer
Cao, C., Gao, R., Zhang, M., Amelio, A. L., Fallahi, M., Chen, Z., Gu, Y., Hu, C., Welsh, E. A., Engel, B. E., et al. (2014) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dju358 · Cited by 44
AG311, a small molecule inhibitor of complex I and hypoxia-induced HIF-1α stabilization
Bastian, A., Matsuzaki, S., Humphries, K. M., Pharaoh, G. A., Doshi, A., Zaware, N., Gangjee, A., & Ihnat, M. A. (2016) · Cancer Letters · doi:10.1016/j.canlet.2016.11.040 · Cited by 43
Inhibition of mTORC1/P70S6K pathway by Metformin synergistically sensitizes Acute Myeloid Leukemia to Ara-C
Yuan, F., Cheng, C., Xiao, F., Liu, H., Cao, S., & Zhou, G. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117276 · Cited by 44
The Tumor Suppressor Kinase LKB1: Metabolic Nexus
Bourouh, M., & Marignani, P. A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.881297 · Cited by 48
AMPK β1 reduces tumor progression and improves survival in p53 null mice
Houde, V. P., Donzelli, S., Sacconi, A., Galić, S., Hammill, J. A., Bramson, J. L., Foster, R. A., Tsakiridis, T. K., Kemp, B. E., Grasso, G., et al. (2017) · Molecular Oncology · doi:10.1002/1878-0261.12079 · Cited by 41
Imaging Cancer Metabolism
Momcilovic, M., & Shackelford, D. B. (2017) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2017.220 · Cited by 42
Self-citation
Co-occurring KRAS mutation/LKB1 loss in non-small cell lung cancer cells results in enhanced metabolic activity susceptible to caloric restriction: an in vitro integrated multilevel approach
Caiola, E., Falcetta, F., Giordano, S., Marabese, M., Garassino, M. C., Broggini, M., Pastorelli, R., & Brunelli, L. (2018) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-018-0954-5 · Cited by 41
Metformin: an old drug with new potential
Hajjar, J., Habra, M. A., & Naing, A. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2013.833604 · Cited by 42
Exploiting FAsting-mimicking Diet and MEtformin to Improve the Efficacy of Platinum-pemetrexed Chemotherapy in Advanced LKB1-inactivated Lung Adenocarcinoma: The FAME Trial
Vernieri, C., Signorelli, D., Galli, G., Ganzinelli, M., Moro, M., Fabbri, A., Tamborini, E., Marabese, M., Caiola, E., Broggini, M., et al. (2018) · Clinical Lung Cancer · doi:10.1016/j.cllc.2018.12.011 · Cited by 41
Ouabain impairs cancer metabolism and activates AMPK-Src signaling pathway in human cancer cell lines
Shen, J., Zhan, Y.-C., Li, H.-Y., & Wang, Z. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0290-0 · Cited by 43
AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis
Wang, Y., Luo, M., Wang, F., Tong, Y., Li, L., Shu, Y., Qiao, K., Zhang, L., Yan, G., Liu, J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34747-y · Cited by 40
Modulation of Bax and mTOR for Cancer Therapeutics
Li, R., Ding, C., Zhang, J., Xie, M., Park, D., Ding, Y., Chen, G., Zhang, G., Gilbert‐Ross, M., Zhou, W., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-16-2356 · Cited by 40
Iron chelation inhibits mTORC1 signaling involving activation of AMPK and REDD1/Bnip3 pathways
Shang, C., Zhou, H., Liu, W., Shen, T., Luo, Y., & Huang, S. (2020) · Oncogene · doi:10.1038/s41388-020-1366-5 · Cited by 43
Synthetic Lethal Vulnerabilities of Cancer
de la Cruz, F. F., Gapp, B. V., & Nijman, S. M. B. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124511 · Cited by 43
Targeting Pathways Downstream of KRAS in Lung Adenocarcinoma
Zhu, Z., Golay, H. G., & Barbie, D. A. (2014) · Pharmacogenomics · doi:10.2217/pgs.14.108 · Cited by 40
Loss of FGL1 induces epithelial‑mesenchymal transition and angiogenesis in LKB1 mutant lung adenocarcinoma
Bie, F., Wang, G., Qu, X. H., Wang, Y., Huang, C., Wang, Y., & Du, J. (2019) · International Journal of Oncology · doi:10.3892/ijo.2019.4838 · Cited by 39
Type 2 Diabetes Mellitus and Cancer: Epidemiology, Physiopathology and Prevention
Rey‐Reñones, C., Baena-Díez, J. M., Aguilar‐Palacio, I., Miquel, C., & Grau, M. (2021) · Biomedicines · doi:10.3390/biomedicines9101429 · Cited by 43
Recent progress in the development of nanomaterials targeting multiple cancer metabolic pathways: a review of mechanistic approaches for cancer treatment
Zhang, L., Zhai, B.-Z., Wu, Y., & Wang, Y. (2023) · Drug Delivery · doi:10.1080/10717544.2022.2144541 · Cited by 39
Metabolic regulator LKB1 controls adipose tissue ILC2 PD-1 expression and mitochondrial homeostasis to prevent insulin resistance
Sun, J., Zhang, Y., Zhang, Q., Hu, L., Zhao, L., Wang, H., Yuan, Y., Niu, H., Wang, D., Zhang, H., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.04.024 · Cited by 39
Managing lipid metabolism in proliferating cells: New perspective for metformin usage in cancer therapy
Lettieri‐Barbato, D., Vegliante, R., Desideri, E., & Ciriolo, M. R. (2014) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2014.02.003 · Cited by 39
Cardiac glycosides display selective efficacy for STK11 mutant lung cancer
Kim, N., Yim, H. Y., He, N., Lee, C., Kim, J.-H., Choi, J., Lee, H. S., Kim, S., Jeong, E., Song, M., et al. (2016) · Scientific Reports · doi:10.1038/srep29721 · Cited by 38
Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer
Hassanabad, A. F., & MacQueen, K. T. (2020) · Cellular Oncology · doi:10.1007/s13402-020-00570-0 · Cited by 40
Cancer Stem Cells: Metabolic Characterization for Targeted Cancer Therapy
Kaur, J., & Bhattacharyya, S. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.756888 · Cited by 38
Metformin with Everolimus and Octreotide in Pancreatic Neuroendocrine Tumor Patients with Diabetes
Pusceddu, S., Buzzoni, R., Vernieri, C., Concas, L., Marceglia, S. R. F., Giacomelli, L., Milione, M., Leuzzi, L., Femia, D., Formisano, B., et al. (2016) · Future Oncology · doi:10.2217/fon-2015-0077 · Cited by 38
Environmental Stress Affects the Activity of Metabolic and Growth Factor Signaling Networks and Induces Autophagy Markers in MCF7 Breast Cancer Cells
Casado, P., Bilanges, B., Rajeeve, V., Vanhaesebroeck, B., & Cutillas, P. R. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.034751 · Cited by 37
Metformin Triggers Autophagy to Attenuate Drug-Induced Apoptosis in NSCLC Cells, with Minor Effects on Tumors of Diabetic Patients
Xiao, Z., Gaertner, S., Morresi‐Hauf, A., Genzel, R., Duell, T., Ullrich, A., & Knyazev, P. G. (2017) · Neoplasia · doi:10.1016/j.neo.2017.02.011 · Cited by 37
Oxidative stress-mediated AMPK inactivation determines the high susceptibility of LKB1-mutant NSCLC cells to glucose starvation
Ren, Y., Chen, J., Chen, P., Hao, Q., Cheong, L.-K., Tang, M., Hong, L., Hu, X., Yap, C. T., Bay, B., et al. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.02.018 · Cited by 41
Diabetes and Its Link with Cancer: Providing the Fuel and Spark to Launch an Aggressive Growth Regime
Joshi, S., Liu, M., & Turner, N. A. (2015) · BioMed Research International · doi:10.1155/2015/390863 · Cited by 36
Synthetic lethality in lung cancer and translation to clinical therapies
Leung, A. W. Y., de Silva, T., Bally, M. B., & Lockwood, W. W. (2016) · Molecular Cancer · doi:10.1186/s12943-016-0546-y · Cited by 35
Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells
Ye, T., Su, J., Huang, C., Yu, D., Dai, S., Huang, X., Chen, B., & Zhou, M. (2016) · OncoTargets and Therapy · doi:10.2147/ott.s122653 · Cited by 37
The Liver Circadian Clock Modulates Biochemical and Physiological Responses to Metformin
Henriksson, E., Huber, A., Soto, E., Kriebs, A., Vaughan, M. E., Duglan, D., Chan, A. B., Papp, S. J., Nguyen, M., Afetian, M. E., et al. (2017) · Journal of Biological Rhythms · doi:10.1177/0748730417710348 · Cited by 37
AMPK-Independent LKB1 Activity Is Required for Efficient Epithelial Ovarian Cancer Metastasis
Buensuceso, A. V., Ramos-Valdes, Y., DiMattia, G. E., & Shepherd, T. G. (2019) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-19-0530 · Cited by 35
2016: A ‘Mitochondria’ Odyssey
Cherry, C. J., Thompson, B. S., Saptarshi, N., Wu, J., & Hoh, J. J. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.03.009 · Cited by 34
RAS signaling and anti-RAS therapy: lessons learned from genetically engineered mouse models, human cancer cells, and patient-related studies
Fang, B. (2015) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmv090 · Cited by 37
Gemcitabine and Chk1 Inhibitor AZD7762 Synergistically Suppress the Growth of Lkb1-Deficient Lung Adenocarcinoma
Liu, Y., Li, Y., Wang, X., Liu, F., Gao, P., Quinn, M. M., Li, F., Merlino, A. A., Benes, C., Liu, Q., et al. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0567 · Cited by 33
AMP-activated protein kinase and energy balance in breast cancer.
Zhao, H., Orhan, Y. C., Zha, X., Esencan, E., Chatterton, R. T., & Bulun, S. E. (2017) · Europe PMC (PubMed Central) · Cited by 35
Discovery of Small Molecule Bak Activator for Lung Cancer Therapy
Park, D., Anisuzzaman, A. S. M., Magis, A. T., Chen, G., Xie, M., Zhang, G., Behera, M., Sica, G., Ramalingam, S. S., Owonikoko, T. K., et al. (2021) · Theranostics · doi:10.7150/thno.60349 · Cited by 32
Associations between body mass index, weight loss and overall survival in patients with advanced lung cancer
Oswalt, C. J., Liu, Y., Pang, H., Le‐Rademacher, J. G., Wang, X., & Crawford, J. (2022) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13095 · Cited by 32
Mitochondria and CancerPreprint
Kenny, T. C., & Birsoy, K. (2024) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a041534 · Cited by 40
MATE2 Expression Is Associated With Cancer Cell Response to Metformin
Chowdhury, S., Yung, E., Pintilie, M., Muaddi, H., Chaib, S., Yeung, M., Fusciello, M., Sykes, J., Pitcher, B., Hagenkort, A., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0165214 · Cited by 33
Genomic profiling toward precision medicine in non-small cell lung cancer: getting beyond EGFR
Whitsett, T. G., Richer, A. L., Friel, J. M., Carson, V. M., & Inge, L. J. (2015) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s52845 · Cited by 35
Therapeutic Effects of Repurposed Therapies in Non-Small Cell Lung Cancer: What Is Old Is New Again
Saxena, A., Becker, D. J., Preeshagul, I. R., Lee, K. S., Katz, E., & Levy, B. P. (2015) · The Oncologist · doi:10.1634/theoncologist.2015-0064 · Cited by 34
AMPK-mediated energy homeostasis and associated metabolic effects on cancer cell response and resistance to cetuximab
Li, X., Lü, Y., Lu, H., Luo, J., Hong, Y. K., & Fan, Z. (2015) · Oncotarget · doi:10.18632/oncotarget.3432 · Cited by 32
Repression of LKB1 by miR-17∼92 Sensitizes MYC-Dependent Lymphoma to Biguanide Treatment
Izreig, S., Gariepy, A., Kaymak, I., Bridges, H. R., Donayo, A. O., Bridon, G., DeCamp, L. M., Kitchen-Goosen, S. M., Avizonis, D. Z., Sheldon, R. D., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100014 · Cited by 31
Intrinsic strategies for the evasion of cGAS-STING signaling-mediated immune surveillance in human cancer: How therapy can overcome them
Zou, S.-S., Qiao, Y., Zhu, S., Gao, B., Yang, N., Liu, Y.-J., & Chen, J. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105514 · Cited by 32
Unravelling the connection between metabolism and tumorigenesis through studies of the liver kinase B1 tumour suppressor
Shackelford, D. B. (2013) · Journal of Carcinogenesis · doi:10.4103/1477-3163.116323 · Cited by 31
Self-citation
Phenformin has anti-tumorigenic effects in human ovarian cancer cells and in an orthotopic mouse model of serous ovarian cancer
Jackson, A. L., Sun, W., Kilgore, J., Guo, H., Fang, Z., Yin, Y., Jones, H. M., Gilliam, T. P., Zhou, C., & Bae-Jump, V. L. (2017) · Oncotarget · doi:10.18632/oncotarget.22012 · Cited by 34
Role of INSL4 Signaling in Sustaining the Growth and Viability of LKB1-Inactivated Lung Cancer
Yang, R., Li, S. W., Chen, Z., Zhou, X., Wei Min, N. I., Fu, D., Lu, J., Kaye, F. J., & Wu, L. (2018) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djy166 · Cited by 28
Long term treatment of metformin impedes development of chemoresistance by regulating cancer stem cell differentiation through taurine generation in ovarian cancer cells
Bishnu, A., Sakpal, A., Ghosh, N., Choudhury, P., Chaudhury, K., & Ray, P. (2018) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2018.12.016 · Cited by 31
Repurposing drugs targeting metabolic diseases for cancer therapeutics
Pillai U, J., Ray, A., Maan, M., & Dutta, M. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103684 · Cited by 31
A Transcriptional Signature Identifies LKB1 Functional Status as a Novel Determinant of MEK Sensitivity in Lung Adenocarcinoma
Kaufman, J. M., Yamada, T., Park, K., Timmers, C. D., Amann, J. M., & Carbone, D. P. (2016) · Cancer Research · doi:10.1158/0008-5472.can-16-1639 · Cited by 31
IKK promotes cytokine-induced and cancer-associated AMPK activity and attenuates phenformin-induced cell death in LKB1-deficient cells
Antonia, R. J., & Baldwin, A. S. (2018) · Science Signaling · doi:10.1126/scisignal.aan5850 · Cited by 30
Tumor Milieu Controlled by RB Tumor Suppressor
Kitajima, S., Li, F., & Takahashi, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072450 · Cited by 30
New approach of delivering cytotoxic drugs towards CAIX expressing cells: A concept of dual-target drugs
van Kuijk, S. J. A., Parvathaneni, N. K., Niemans, R., van Gisbergen, M. W., Carta, F., Vullo, D., Pastoreková, S., Yaromina, A., Supuran, C. T., Dubois, L. J., et al. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.10.037 · Cited by 29
Results from 11C-metformin-PET scans, tissue analysis and cellular drug-sensitivity assays questions the view that biguanides affects tumor respiration directly
Iversen, A. B. B., Horsman, M. R., Jakobsen, S., Jensen, J., Garm, C., Jessen, N., Breining, P., Frøkiær, J., & Busk, M. (2017) · Scientific Reports · doi:10.1038/s41598-017-10010-z · Cited by 29
The Role of AMPK/mTOR Modulators in the Therapy of Acute Myeloid Leukemia
Višnjić, D., Dembitz, V., & Lalić, H. (2018) · Current Medicinal Chemistry · doi:10.2174/0929867325666180117105522 · Cited by 28
Emerging strategies to target cancer metabolism and improve radiation therapy outcomes
Kery, M., & Papandreou, I. (2020) · British Journal of Radiology · doi:10.1259/bjr.20200067 · Cited by 33

Authors: Shackelford, D. B., Abt, E., Gerken, L., Vasquez, D. S., Seki, A., Leblanc, M., Wei, L., Fishbein, M. C., Czernin, J., Mischel, P. S., & Shaw, R. J.
Affiliations: Salk Institute for Biological Studies (US)
University of California, Los Angeles (US)
Corresponding author: Shackelford, David B.
Shaw, Reuben J.
ORCID: Shackelford, David B.
Abt, Evan
Leblanc, Mathias
Fishbein, Michael C.
Mischel, Paul S.
Shaw, Reuben J.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2013-02
Volume: 23
Issue: 2
Pages: 143-158
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2012.12.008
PMC: PMC3579627
OpenAlex: W2135617839
Cited by: 585
References: 53
Citations by year: 2026: 19 · 2025: 22 · 2024: 32 · 2023: 34 · 2022: 33 · 2021: 53 · 2020: 46 · 2019: 45 · 2018: 46 · 2017: 58 · 2016: 44 · 2015: 62 · 2014: 54 · 2013: 36
FWCI: 29.29
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 382 d)
Locations: Cancer Cell (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (UL1TR000124, KL2TR000122)
National Cancer Institute (R01CA172229, P01CA120964, T32CA009370, P30CA014195)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080425)
National Center for Research Resources (S10RR026744)
National Center for Advancing Translational Sciences
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords: LKB1, STK11, non-small cell lung cancer, phenformin, cancer metabolism, AMPK, mitochondrial inhibition, apoptosis, KRAS mutation, TP53 mutation, tumor suppressor inactivation, metabolic therapy
MeSH terms: Animals, Carcinoma, Non-Small-Cell Lung, Cells, Cultured, Humans, Hypoglycemic Agents, Lung Neoplasms, Mitochondria, Mutation, Phenformin, RNA, Messenger, Blotting, Western, Eukaryotic Initiation Factor-2, Tumor Suppressor Protein p53, Proto-Oncogene Proteins p21(ras), Apoptosis, Protein Serine-Threonine Kinases, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Cell Proliferation, Mice, AMP-Activated Protein Kinases, Real-Time Polymerase Chain Reaction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

LKB1 Inactivation Dictates Therapeutic Response of Non-Small Cell Lung Cancer to the Metabolism Drug Phenformin

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks