ArticlePloS one2013
Loss of LKB1 expression reduces the latency of ErbB2-mediated mammary gland tumorigenesis, promoting changes in metabolic pathways.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Metabolic permissiveness: how tissue context shapes cancer.Genes & development · 2026Review
- Review
- Oncogenic metabolic reprogramming in breast cancer: focus on signaling pathways and mitochondrial genes.Medical oncology (Northwood, London, England) · 2023Review
- Exploring potential molecular resistance and clonal evolution in advanced HER2-positive gastric cancer under trastuzumab therapy.Oncogenesis · 2023Article
- The Tumor Suppressor Kinase LKB1: Metabolic Nexus.Frontiers in cell and developmental biology · 2022Review
- Review
- STK11 alterations in the pan-cancer setting: prognostic and therapeutic implications.European journal of cancer (Oxford, England : 1990) · 2021Article
- The Metabolic Mechanisms of Breast Cancer Metastasis.Frontiers in oncology · 2020Review
- Liver Kinase B1-A Potential Therapeutic Target in Hormone-Sensitive Breast Cancer in Older Women.Cancers · 2019Article
- Sputum Detection of Predisposing Genetic Mutations in Women with Pulmonary Nontuberculous Mycobacterial Disease.Scientific reports · 2018Article
- Ranitidine Inhibition of Breast Tumor Growth Is B Cell Dependent and Associated With an Enhanced Antitumor Antibody Response.Frontiers in immunology · 2018Article
- Article
- Article
- The glucose transporter GLUT1 is required for ErbB2-induced mammary tumorigenesis.Breast cancer research : BCR · 2016Article
- Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice.Oncoimmunology · 2016Article
- Clinical Relevance of Liver Kinase B1(LKB1) Protein and Gene Expression in Breast Cancer.Scientific reports · 2016Article
- Activation of the AMPK-ULK1 pathway plays an important role in autophagy during prion infection.Scientific reports · 2015Article
- Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression.Carcinogenesis · 2015Review
- Rewiring cell polarity signaling in cancer.Oncogene · 2015Review
- Pre-clinical study of drug combinations that reduce breast cancer burden due to aberrant mTOR and metabolism promoted by LKB1 loss.Oncotarget · 2014Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The tumor suppressor kinase LKB1 is mutated in a broad range of cancers however, the role of LKB1 mammary gland tumorigenesis is not fully understood. Evaluation of human breast cancer tissue microarrays, indicate that 31% of HER2 positive samples lacked LKB1 expression. To expand on these observations, we crossed STK11 (fl/fl) mice with mice genetically engineered to express activated Neu/HER2-MMTV-Cre (NIC) under the endogenous Erbb2 promoter, to generate STK11 (-/-/) NIC mice. In these mice, the loss of lkb1 expression reduced the latency of ErbB2-mediated tumorigenesis compared to the latency of tumorigenesis in NIC mice alone. Analysis of STK11(-/-/)NIC mammary tumors revealed hyperactivation of mammalian target of rapamycin (mTOR) through both mTORC1 and mTORC2 pathways as determined by the phosphorylation status of ribosomal protein S6 and AKT. Furthermore, STK11(-/-/)NIC mammary tumors had elevated ATP levels along with changes in metabolic enzymes and metabolites. The treatment of primary mammary tumor cells with specific mTOR inhibitors AZD8055 and Torin1, that target both mTOR complexes, attenuated mTOR activity and decreased expression of glycolytic enzymes. Our findings underscore the existence of a molecular interplay between LKB1-AMPK-mTORC1 and ErbB2-AKT-mTORC2 pathways with mTOR at its epicenter, suggestive that loss of LKB1 expression may serve as a marker for hyperactivated mTOR in HER2 positive breast cancer and warranting further investigation into therapeutics that target LKB1-AMPK-mTOR and glycolytic pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.