Controlling the master—upstream regulation of the tumor suppressor LKB1
Abstract
The tumor suppressor LKB1 is an essential serine/threonine kinase, which regulates various cellular processes such as cell metabolism, cell proliferation, cell polarity, and cell migration. Germline mutations in the STK11 gene (encoding LKB1) are the cause of the Peutz-Jeghers syndrome, which is characterized by benign polyps in the intestine and a higher risk for the patients to develop intestinal and extraintestinal tumors. Moreover, mutations and misregulation of LKB1 have been reported to occur in most types of tumors and are among the most common aberrations in lung cancer. LKB1 activates several downstream kinases of the AMPK family by direct phosphorylation in the T-loop. In particular the activation of AMPK upon energetic stress has been intensively analyzed in various diseases, including cancer to induce a metabolic switch from anabolism towards catabolism to regulate energy homeostasis and cell survival. In contrast, the regulation of LKB1 itself has long been only poorly understood. Only in the last years, several proteins and posttranslational modifications of LKB1 have been analyzed to control its localization, activity and recognition of substrates. Here, we summarize the current knowledge about the upstream regulation of LKB1, which is important for the understanding of the pathogenesis of many types of tumors.
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LKB1 is a master kinase that regulates diverse cellular processes via phosphorylation of multiple members of AMPK family kinases.
“LKB1 is a master kinase that regulates diverse cellular processes via phosphorylation of multiple members of AMPK family kinases45,65.”
From LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers (2025) · cites this paper as [65]
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Loss of Cytoplasmic Retention Ability of Mutant LKB1 Found in Peutz-Jeghers Syndrome Patients
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Complexity of the Wnt/β‑catenin pathway: Searching for an activation model
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Mutation of Lkb1 and p53 Genes Exert a Cooperative Effect on Tumorigenesis
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LKB1 regulates polarity remodeling and adherens junction formation in the <i>Drosophila</i> eye
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Investigating the Regulation of Brain-specific Kinases 1 and 2 by Phosphorylation
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Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK–LKB1 Signaling Axis
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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 · see citing works
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The Par3-like polarity protein Par3L is essential for mammary stem cell maintenance
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Self-citationCharacterization of an Alternative Splice Variant of LKB1
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Isoform-specific Regulation of Akt Signaling by the Endosomal Protein WDFY2
Walz, H. A., Shi, X., Chouinard, M., Bue, C. A., Navaroli, D. M., Hayakawa, A., Zhou, Q. L., Nadler, J., Leonard, D. M., & Corvera, S. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.110536 · Cited by 41 · see citing works
George, S. H. L., Milea, A. L., Sowamber, R., Chehade, R., Tone, A. A., & Shaw, P. A. (2015) · Oncogene · doi:10.1038/onc.2015.62 · Cited by 37 · see citing works
Bultot, L., Horman, S., Neumann, D., Walsh, M. P., Hue, L., & Rider, M. H. (2008) · FEBS Letters · doi:10.1016/j.febslet.2008.11.022 · Cited by 37 · see citing works
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O’Farrell, F., Lobert, V. H., Sneeggen, M., Jain, A., Katheder, N. S., Wenzel, E. M., Schultz, S. W., Tan, K. W., Brech, A., Stenmark, H., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3631 · Cited by 29 · see citing works
Korsse, S. E., Biermann, K., Offerhaus, G. J. A., Wagner, A., Dekker, E., Mathus-Vliegen, E. M. H., Kuipers, E. J., van Leerdam, M. E., & van Veelen, W. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt068 · Cited by 27 · see citing works
Par3L enhances colorectal cancer cell survival by inhibiting Lkb1/AMPK signaling pathway
Li, T., Liu, D., Lei, X., & Jiang, Q. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.11.154 · Cited by 27 · see citing works
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Liu, Z., Dai, X., Zhu, H., Zhang, M., & Zou, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.649210 · Cited by 24 · see citing works
Bai, Y., Zhou, T., Fu, H., Sun, H., & Huang, B. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.03.018 · Cited by 18 · see citing works
Liu, L., Siu, F., Che, C., Xu, A., & Wang, Y. (2012) · Europe PMC (PubMed Central) · Cited by 17 · see citing works
LKB1 Controls the Pluripotent State of Human Embryonic Stem Cells
Lai, D., Chen, Y., Wang, F., Jiang, L., & Wei, C. (2012) · Cellular Reprogramming · doi:10.1089/cell.2011.0068 · Cited by 16 · see citing works
Coordinated cell motility is regulated by a combination of LKB1 farnesylation and kinase activity
Wilkinson, S. C., Hou, Y., Zoine, J. T., Saltz, J. H., Zhang, C., Chen, Z., Cooper, L., & Marcus, A. I. (2017) · Scientific Reports · doi:10.1038/srep40929 · Cited by 10 · see citing works
Cidlinsky, N. A., Dogliotti, G., Pukrop, T., Jung, R., Weber, F., & Krahn, M. P. (2016) · Cellular Oncology · doi:10.1007/s13402-016-0290-8 · Cited by 6 · see citing works
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Regulating tumor suppressor genes: post-translational modifications
Chen, L., Liu, S., & Tao, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0196-9 · Cited by 449 · see citing works
Signaling networks in immunometabolism
Saravia, J., Raynor, J. L., Chapman, N. M., Lim, S. A., & Chi, H. (2020) · Cell Research · doi:10.1038/s41422-020-0301-1 · Cited by 252 · see citing works
Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential
Wein, M. N., Foretz, M., Fisher, D. E., Xavier, R. J., & Kronenberg, H. M. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.08.004 · Cited by 138 · see citing works
“Since LKB1 is the best-known SIK activator [2], it is possible that signals that induce LKB1 function [17] may also increase SIK activity.”
BackgroundTachecí, I., Kopáčová, M., & Bureš, J. (2021) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000718 · Cited by 104 · see citing works
“proliferation, migration, DNA damage response and p53-mediated programmed cell death (apoptosis) promotion [15].”
An LKB1–mitochondria axis controls TH17 effector function
Baixauli, F., Piletič, K., Puleston, D. J., Villa, M., Field, C. S., Flachsmann, L. J., Quintana, A., Rana, N., Edwards-Hicks, J., Matsushita, M., et al. (2022) · Nature · doi:10.1038/s41586-022-05264-1 · Cited by 100 · see citing works
Tankyrases as modulators of pro-tumoral functions: molecular insights and therapeutic opportunities
Zamudio-Martínez, E., Herrera-Campos, A. B., Múñoz, A., Rodríguez-Vargas, J. M., & Oliver, F. J. (2021) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-01950-6 · Cited by 57 · see citing works
“However, the loss of RNF146 enhances the phosphorylation of LKB1 at Ser428, the activation of AMPK, but does not alter LKB1 protein levels.”
BackgroundInfluentialThe Therapeutic Potential of DNA Damage Repair Pathways and Genomic Stability in Lung Cancer
Burgess, J. T., Rose, M., Boucher, D., Plowman, J., Molloy, C., Fisher, M. A., O’Leary, C. G., Richard, D. J., O'Byrne, K. J., & Bolderson, E. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01256 · Cited by 53 · see citing works
Zhang, Z.-J., Yuan, J., Bi, Y., Wang, C., & Liu, Y. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.01.036 · Cited by 47 · see citing works
Lemos, C., Schulze, V., Baumgart, S. J., Nevedomskaya, E., Heinrich, T. K., Lefranc, J., Bader, B., Christ, C. D., Briem, H., Kuhnke, L., et al. (2021) · Cellular Oncology · doi:10.1007/s13402-020-00584-8 · Cited by 46 · see citing works
Zuo, A., Zhao, X., Li, T., Li, J., Lei, S., Chen, J., Xu, D., Song, C., Liu, T., Li, C., et al. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14982 · Cited by 45 · see citing works
Gao, Y., Päivinen, P., Tripathi, S., Domènech-Moreno, E., Wong, I. P. L., Vaahtomeri, K., Nagaraj, A. S., Talwelkar, S. S., Foretz, M., Verschuren, E. W., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-2049 · Cited by 40 · see citing works
“As the landscape of primary resistance to PD-1 immunotherapy in LUAD is not fully understood and the current approaches to investigate loss of LKB1 by mutation screens (37) or LKB1 staining (2) may not be comprehensive due to nongenomic alterations (38) or defects in cofactors required for LKB1 function (39), there is…”
BackgroundThe Importance of STK11/LKB1 Assessment in Non-Small Cell Lung Carcinomas
Mograbi, B., Heeke, S., & Hofman, P. M. (2021) · Diagnostics · doi:10.3390/diagnostics11020196 · Cited by 39 · see citing works
“Consequently, LKB1 activates several downstream kinases of the AMPK family by direct phosphorylation in the T-loop domain [60].”
BackgroundNi, X., Wang, L., Wang, H., Yu, T., Xie, J., Li, G., Liu, Y., Zhou, H., Xu, M., Hou, M., et al. (2022) · Blood · doi:10.1182/blood.2022016029 · Cited by 34 · see citing works
Induction of STK11-dependent cytoprotective autophagy in breast cancer cells upon honokiol treatment
Muniraj, N., Siddharth, S., Shriver, M., Nagalingam, A., Parida, S., Woo, J., Elsey, J., Gabrielson, K. L., Gabrielson, E. W., Arbiser, J. L., et al. (2020) · Cell Death Discovery · doi:10.1038/s41420-020-00315-w · Cited by 33 · see citing works
Signaling Pathways Involved in Nutrient Sensing Control in Cancer Stem Cells: An Overview
Robles‐Flores, M., Moreno-Londoño, Á. P., & Castañeda‐Patlán, M. C. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.627745 · Cited by 33 · see citing works
“It has been suggested that AMPK possesses tumor suppressor-like activity because, in response to energy stress, it is activated by the upstream kinase LKB1, a tumor suppressor whose function is often lost in human cancers (92).”
BackgroundZebrafish Cancer Predisposition Models
Kobar, K., Collett, K., Prykhozhij, S. V., & Berman, J. N. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.660069 · Cited by 32 · see citing works
“Normally following a metabolic stress event, LKB1 activates AMP-activated protein kinase (AMPK), leading to a signaling cascade that inhibits the mTOR pathway (Figure 3C), thus preventing cell replication and growth in unfavorable conditions (Hardie, 2007; Kullmann and Krahn, 2018).”
BackgroundJung, T.-Y., Ryu, J.-E., Jang, M.-M., Lee, S.-Y., Jin, G.-R., Kim, C., Lee, C., Kim, H., Kim, E., Park, S., et al. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00525-3 · Cited by 26 · see citing works
Phospholipids of the Plasma Membrane – Regulators or Consequence of Cell Polarity?
Krahn, M. P. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00277 · Cited by 26 · see citing works
Self-citationMorelli, A. P., Tortelli, T. C., Pavan, I. C. B., Silva, F. R., Granato, D. C., Peruca, G. F., Pauletti, B. A., Domingues, R. R., Bezerra, R. M. N., de Moura, L. P., et al. (2021) · International Journal of Oncology · doi:10.3892/ijo.2021.5208 · Cited by 25 · see citing works
Weidle, U. H., Birzele, F., & Nopora, A. (2019) · Cancer Genomics & Proteomics · doi:10.21873/cgp.20149 · Cited by 21 · see citing works
Zyla, R. E., Hahn, E., & Hodgson, A. (2021) · Journal of Clinical Pathology · doi:10.1136/jclinpath-2021-207906 · Cited by 20 · see citing works
Li, Q., Yang, Y., Wang, H. H., Jiang, Z., & Ma, H. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120676 · Cited by 20 · see citing works
MDM2-mediated ubiquitination of LKB1 contributes to the development of diabetic cataract
Li, X., Sun, X., Li, L., Luo, Y., Chi, Y., & Zheng, G. (2022) · Experimental Cell Research · doi:10.1016/j.yexcr.2022.113191 · Cited by 18 · see citing works
Noristani, H. N. (2022) · Experimental Neurology · doi:10.1016/j.expneurol.2022.114198 · Cited by 18 · see citing works
O’Neill, E. J., Sze, S. K., MacPherson, R. E. K., & Tsiani, E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25041950 · Cited by 18 · see citing works
“The phosphorylation of LKB1 at the Ser 428 residue mediates its association with, and the activation of AMPK [30].”
BackgroundNegative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer
Figueroa‐González, G., Carrillo, J. F., Perez-Rodriguez, I., de León, D. F. C., Campos-Parra, A. D., Martínez-Gutiérrez, A. D., Coronel-Hernández, J., García-Castillo, V., López‐Camarillo, C., Peralta-Zaragoza, Ó., et al. (2020) · Genes · doi:10.3390/genes11091058 · Cited by 16 · see citing works
“The function of LKB1 is regulated by diverse mechanisms in different types of tumors, with loss of heterozygosity LOH [26], somatic mutations that inactivate the function of the protein (for an extensive review [27]), and hyper-methylation in the promoter region of the gene [28,29] having been observed.”
BackgroundGeographical, ethnic, and genetic differences in pancreatic cancer predisposition
Liew, S. Z. H., Ng, K. W., Ishak, N. D. B., Lee, S. Y., Zhang, Z., Chiang, J., & Ngeow, J. Y. Y. (2023) · Chinese Clinical Oncology · doi:10.21037/cco-23-8 · Cited by 14 · see citing works
AMPK: An energy sensor for non-small cell lung cancer progression and treatment
Zhong, Z.-T., Wang, X., Pan, Y., Zhou, K., Chen, J.-H., Gao, Y., Dai, B., Zhou, Z., & Wang, R. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107592 · Cited by 15 · see citing works
Chen, S., Li, J., Ye, L., Zhang, M., Qiu, Z., Liu, S., Wang, H., Zhu, Y., Song, S., Hou, X., et al. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07154-y · Cited by 13 · see citing works
“Truly, a recent study found Sumoylated LKB1 precisely controls AMPK activation [19].”
LKB1 expression and the prognosis of lung cancer
Lin, C., Lin, X., Lin, K., Tan, J., Wei, C., & Liu, T. (2021) · Medicine · doi:10.1097/md.0000000000027841 · Cited by 13 · see citing works
“Discussion The cancer suppressor LKB1 is an essential serine/threonine kinase, which induces multifarious cellular processes such as cell metabolism, cell proliferation and cell migration.([25]) Somatic mutations or loss-of-function alterations of LKB1 were found in different tumor types, such as cervical carcinoma, b…”
BackgroundYang, C., Ding, H., Yang, Y., Yang, L., Yang, Y., Fang, M., Ren, J., Hu, R., Wang, C., & Geng, W. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.05.223 · Cited by 12 · see citing works
Anticarcinogenic Effects of Gold Nanoparticles and Metformin Against MCF-7 and A549 Cells
Yeşildağ, A., Kızıloğlu, H. T., Dirican, E., Erbaş, E., Gelen, V., & Kara, A. (2024) · Biological Trace Element Research · doi:10.1007/s12011-024-04090-y · Cited by 11 · see citing works
“Some chemotherapy drugs, including doxorubicin, cyclophosphamide, and paclitaxel, work like conventional cancer treatments by causing the tumor cells to die in an immune-mediated manner [36, 82].”
BackgroundLKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS-mutant lung cancers
Li, C., Syed, M. U., Nimbalkar, A., Shen, Y., Vieira, M. D., Fraser, C., Inde, Z., Qin, X., Ouyang, J., Kreuzer, J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-58753-y · Cited by 11 · see citing works
“LKB1 is a master kinase that regulates diverse cellular processes via phosphorylation of multiple members of AMPK family kinases 45,65 .”
The metabolic sensor LKB1 regulates ILC3 homeostasis and mitochondrial function
Fonseca‐Pereira, D., Bae, S., Clay, S. L., Michaud, M., MacDonald, M. H., Glickman, J. N., & Garrett, W. S. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.115456 · Cited by 10 · see citing works
Borkowsky, S., Gass, M., Alavizargar, A., Hanewinkel, J., Hallstein, I., Nedvetsky, P. I., Heuer, A., & Krahn, M. P. (2023) · Cells · doi:10.3390/cells12050812 · Cited by 10 · see citing works
“Apart from formation of this trimeric complex, several posttranslational modifications have been found to regulate the activity of the LKB1 complex [18].”
BackgroundSelf-citationEvolutionary history of Mo25 gene in plants, a component of RAM/MOR signaling network
Bizotto, F. M., Ceratti, R. S., Braz, A. S. K., & Masuda, H. P. (2018) · Mechanisms of Development · doi:10.1016/j.mod.2018.09.001 · Cited by 10 · see citing works
Ren, Y., Zhao, F., Mo, H., Jia, R. R., Tang, J., Zhao, X. H., Wei, J. L., Huo, R. R., Li, Q. Q., & You, X. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-027185 · Cited by 10 · see citing works
Type II Binders Targeting the “GLR-Out” Conformation of the Pseudokinase STRADα
Smith, R. H. B., Khan, Z. M., Ung, P. M. U., Scopton, A. P., Silber, L., Mack, S. M., Real, A. M., Schlessinger, A., & Dar, A. C. (2021) · Biochemistry · doi:10.1021/acs.biochem.0c00714 · Cited by 8 · see citing works
Endocannabinoid biosynthetic enzymes regulate pain response via LKB1–AMPK signaling
Chen, M., Shin, M., Ware, T. B., Donvito, G., Muchhala, K. H., Mischel, R. A., Mustafa, M. A., Serbulea, V., Upchurch, C. M., Leitinger, N., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2304900120 · Cited by 9 · see citing works
Xu, Z., Davies, E. R., Yao, L., Zhou, Y., Li, J., Alzetani, A., Marshall, B. G., Hancock, D. C., Wallis, T., Downward, J., et al. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.06.034 · Cited by 7 · see citing works
“LKB1 is an evolutionarily conserved serine/threonine protein kinase, which acts as an important regulator of cell polarity, proliferation, and cell metabolism in epithelial cells 23 .”
Functions of LKB1 in neural crest development: The story unfolds
Thibert, C., Lucas, A., Billaud, M., Torch, S., Mével‐Aliset, M., & Allard, J. (2023) · Developmental Dynamics · doi:10.1002/dvdy.581 · Cited by 7 · see citing works
Haiquan, H., Huang, Z., Liao, W., Zou, T., Shang, X., & Yu, H. (2023) · Human Cell · doi:10.1007/s13577-023-00950-2 · Cited by 5 · see citing works
“Only recently, several studies have investigated the upstream regulation of LKB1 [48, 49].”
BackgroundSerine threonine kinase 11/liver kinase B1 mutation in sporadic scirrhous-type gastric cancer cells
Nishimura, S., Yashiro, M., Sera, T., Yamamoto, Y., Kushitani, Y., Sugimoto, A., Kushiyama, S., Togano, S., Kuroda, K., Okuno, T., et al. (2020) · Carcinogenesis · doi:10.1093/carcin/bgaa031 · Cited by 5 · see citing works
Menges, C. W., Hassan, D., Cheung, M., Bellacosa, A., & Testa, J. R. (2024) · Current topics in microbiology and immunology · doi:10.1007/82_2024_278 · Cited by 5 · see citing works
Deciphering the critical roles of the AMPK/mTOR signaling pathway in cancer cell metabolism (Review)
Alasadi, A., Fadhil, N. M., & Chen, S. (2025) · World Academy of Sciences Journal · doi:10.3892/wasj.2025.391 · Cited by 5 · see citing works
“AA, amino acid; PL, phospholipid synthesis; mTOR, mammalian target of rapamycin; mTORC, mammalian target of rapamycin complex; PPP, pentose phosphate pathway. bioenvironmental elements (65,66).”
Branch, M. R., Hsu, C. L., Ohnishi, K., Shen, W.-C., Lee, E., Meisenhelder, J., Winborn, B. J., Sopher, B. L., Taylor, J. P., Hunter, T. R., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202201525 · Cited by 4 · see citing works
“Furthermore, whereas SIRT1 deacetylation of LKB1 has been shown to promote LKB1 activation (Lan et al, 2008), LKB1 is in complex with the pseudokinase STRAD α and scaffold protein MO25 (Kullmann & Krahn, 2018), suggesting that these factors may coordinate LKB1 regulation.”
D’Agostino, E., Mastrodomenico, L., Ponzoni, O., Baldessari, C., Piombino, C., Pipitone, S., Vitale, M. G., Sabbatini, R., Dominici, M., & Toss, A. (2024) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2024.102723 · Cited by 4 · see citing works
Avilés‐Salas, A., Díaz-García, D. A., Lara‐Mejía, L., Cardona, A. F., Orozco‐Morales, M., Catalán, R., Hernández‐Pedro, N., Rios-Garcia, E., Ramos-Ramírez, M., & Arrieta, O. G. (2022) · Current Oncology · doi:10.3390/curroncol30010027 · Cited by 4 · see citing works
“mammalian target of rapamycin (mTOR); in turn, its inhibition downregulates angiogenesisrelated factors such as hypoxia-inducible factor 1 (HIF-1) and vascular endothelial growth factor (VEGF), thereby negatively affecting anaerobic glycolysis (Warburg effect) [2,5,6].”
BackgroundPolarity in respiratory development, homeostasis and disease
Tilston-Lünel, A., & Varelas, X. (2023) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/bs.ctdb.2023.02.004 · Cited by 3 · see citing works
Iraqi, M., Bolel, P., Sarkar, R., Bhattacharya, B., Ahmad, M. A., Edri, A., Roisman, L. C., Elkabets, M., Shalata, W., Peled, N., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214054 · Cited by 3 · see citing works
“In NSCLC, mutations in STK11, followed by disruption of AMPK signaling pathways, are frequently observed [95,96].”
BackgroundRen, Y., Chen, J., Mo, X., Yang, Q., Chen, P., Lu, G. X., Tan, H. W. S., Yi, J., Yu, Q., Kim, Y., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/622126 · Cited by 3 · see citing works
“The tumor suppressive functions of LKB1 has been extensively studied (Kullmann and Krahn, 2018; Momcilovic and Shackelford, 2015).”
BackgroundHuang, J., Deng, H., Xiao, S., Lin, Y., Yu, Z., Xu, X., Peng, L., Chao, H., & Zeng, T. (2024) · Environmental Toxicology · doi:10.1002/tox.24333 · Cited by 2 · see citing works
RetractedIP6K1 Rewires LKB1 Signaling to Mediate Hyperglycemic Endothelial Senescence
Xing, C., Shi, L., Zhu, L., Aguirre, T., Qi, J., Chen, Y., Liu, Y., Chin, A. C., Zhu, H., Fiedler, D., et al. (2025) · Diabetes · doi:10.2337/db24-0706 · Cited by 2 · see citing works
Genetic Knowledge of Colorectal Cancer
Kırbıyık, Ö., & Özyılmaz, B. (2020) · Springer eBooks · doi:10.1007/978-3-030-57273-0_24 · Cited by 2 · see citing works
Lemos, C., Schulze, V., Baumgart, S. J., Nevedomskaya, E., Heinrich, T. K., Lefranc, J., Bader, B., Christ, C. D., Briem, H., Kuhnke, L., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-47637/v1 · Cited by 2 · see citing works
Small molecule activation of the tumor suppressor kinase LKB1Preprint
Song, L., Mitchell, D. C., Liu, J., Wang, L., Wang, Z., He, C., Ding, L., Adler, M. J., Turnham, R. E., Kellett, T., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.17.628051 · Cited by 2 · see citing works
Understanding KRAS: mechanisms of resistance and future therapeutic strategies
Khashaba, R. M., Refaat, N. A., Elmorsy, S. E., Ali, F., & Magar, R. W. (2025) · Discover Applied Sciences · doi:10.1007/s42452-025-07959-2 · Cited by 1 · see citing works
Small-molecule activation of the tumor suppressor kinase LKB1 via the pseudokinase STRAD
Song, L., Mitchell, D. C., Liu, J., Leak, L. B., Turnham, R. E., Wang, L., Wang, Z., He, C., Ding, L., Adler, M., et al. (2026) · Cell chemical biology · doi:10.1016/j.chembiol.2026.07.013 · Cited by 3 · see citing works
LKB1: Controlling Quiescence and Genomic Integrity at Home
Berasain, C., & Avila, M. A. (2018) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2018.03.017 · Cited by 1 · see citing works
Cell Signaling and Translational Developmental Therapeutics
Dent, P. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.00002-5 · Cited by 1 · see citing works
Cell Signaling and Translational Developmental Therapeutics
Dent, P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820472-6.99997-3 · Cited by 1 · see citing works
LKB1 regulates JNK-dependent stress signaling and apoptotic dependency of KRAS -mutant lung cancersPreprint
Li, C., Syed, M. U., Nimbalkar, A., Shen, Y., Fraser, C., Inde, Z., Qin, X., Ouyang, J., Kreuzer, J., Clark, S. E., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.29.510137 · Cited by 1 · see citing works
Metabolic Deregulations in Acute Myeloid Leukemia
Mossuz, P., Chevalier, S., & Mondet, J. (2021) · Vide Leaf, Hyderabad eBooks · doi:10.37247/imcac.1.2021.3
Faculty Opinions recommendation of Signaling networks in immunometabolism.
Kane, L. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.737610223.793578145
Gao, Y., Päivinen, P., Tripathi, S., Domènech‐Moreno, E., Wong, I. P. L., Vaahtomeri, K., Nagaraj, A. S., Talwelkar, S. S., Foretz, M., Verschuren, E. W., et al. (2023) · doi:10.1158/1078-0432.c.6531086
Gao, Y., Päivinen, P., Tripathi, S., Domènech‐Moreno, E., Wong, I. P. L., Vaahtomeri, K., Nagaraj, A. S., Talwelkar, S. S., Foretz, M., Verschuren, E. W., et al. (2023) · doi:10.1158/1078-0432.c.6531086.v1
Lin, X., & Gao, F. (2025) · Biochemical Genetics · doi:10.1007/s10528-025-11040-3
“LKB1 gene expression has been reported to be regulated by several miRNAs, including miR-93, −96, −34a, −34c, −214, −33a, −30b, −145, −182, −30c, −183, −29b, −29c, −153, −138, −451, −195, −17, and −155 under various conditions (Chen et al. 2012; Boldrini et al. 2018; Kullmann and Krahn 2018).”
Maso, A. D., Ferrarini, F., Esposito, G., Minuzzo, S. A., Puggia, A. M., Pezzuto, F., Zulato, E., Bao, L. C., Nuzzo, M. D., Ferro, A., et al. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1552506
Lucas, A., Appaix, F., Allard, J., Mével‐Aliset, M., Radu, A. G., Fauvelle, F., Favier, B., Grichine, A., Maurer, J., Hainaut, P. L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.10.658770
Co-occurrence of Peutz-Jeghers syndrome and unilateral multicystic dysplastic kidney: a case report.
Liu, Y., Hu, S., Gan, Y., & Fang, Y. (2025) · PubMed Central · doi:10.1186/s12882-025-04340-8
“…kinase [11, 12] that regulates the activity of members of the AMP-activated protein kinase (AMPK) family, thereby influencing critical cellular processes such as cell polarity, metabolism, and apoptosis, which can ultimately lead to abnormalities in cell growth and differentiation [13].”
Microtubule affinity-regulating kinases in neurodegenerative disorders
Shahwan, M. J., Anwar, S., Alrouji, M., AlOmeir, O., Dinislam, K., & Shamsi, A. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-44173-8.00014-0
LKB1 functions as a checkpoint for neuronal–glial balance during enteric nervous system developmentPreprint
Lucas, A., Appaix, F., Allard, J., Mével‐Aliset, M., Radu, A. G., Fauvelle, F., Favier, B., Grichine, A., Maurer, J., Hainaut, P. L., et al. (2026) · Genes & Development · doi:10.1101/gad.353358.125
Taneja, N., Chauhan, A., & Singh, S. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-27544-9.00032-5
- Authors
- Kullmann, L., & Krahn, M. P.
- Affiliations
- University Hospital Münster (DE)
- Corresponding author
- Krahn, Michael P.
- ORCID
- Krahn, Michael P.
- Venue
- Oncogene
- Published
- 2018-03-15
- Volume
- 37
- Issue
- 23
- Pages
- 3045-3057
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2791774324
- Cited by
- 75
- References
- 122
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 7 · 2023: 11 · 2022: 8 · 2021: 13 · 2020: 15 · 2019: 4 · 2018: 3
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Keywords
- LKB1, STK11, tumor suppressor, upstream regulation, post-translational modification, AMPK, T-loop phosphorylation, energy homeostasis, metabolic switch, Peutz-Jeghers syndrome, lung cancer, cell polarity, cell migration, cell proliferation
- MeSH terms
- AMP-Activated Protein Kinase Kinases, Allyl Compounds, Biphenyl Compounds, Calcium-Binding Proteins, Humans, Lung Neoplasms, Lysosomes, Mutation, Peutz-Jeghers Syndrome, Phenols, Phosphorylation, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Protein Serine-Threonine Kinases, Lignans, Ubiquitination, AMP-Activated Protein Kinases, Sumoylation
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