Alexandra C. Newton
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Alexandra C. Newton has a total of 361 co-authors. Here are the top co-authors by number of shared publications:
- John Brognard
Department of Surgery, Pharmacology, and Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA
27 shared publications - Aamna Siddiqui
National Cancer Institute at Frederick 3 Laboratory of Cell and Developmental Signaling, Center for Cancer Research National Institutes of Health, Frederick, Maryland
21 shared publications - Amy L. Funk
Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute at Frederick, National Institutes of Health, Frederick, MD, 21702, USA
21 shared publications - Anna A. Marusiak
Laboratory of Molecular OncoSignalling, IMol Polish Academy of Sciences, Warsaw, Poland
21 shared publications - Carolyn C. Woodroofe
Chemistry and Synthesis Center, National Heart, Lung and Blood Institute, Bethesda, MD, 20814
21 shared publications - Eleanor W. Trotter
Cell Division Group, CRUK Manchester Institute, The University of Manchester, Manchester, UK
21 shared publications
Latest Publications
- Open Access
- 3 November 2026
- Published by American Association for Cancer Research (AACR)
Data from Suppression of AKT Activation through LZK Inhibition Limits Tumor Growth in Esophageal and Head and Neck Cancers
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers worldwide due to its aggressive nature and lack of knowledge of underlying oncogenic drivers, limiting treatment options. Approximately 60% of ESCC cases have amplification/overexpression of MAP3K13, which encodes the kinase LZK. In this study, we found that MAP3K13-amplified ESCC exhibits therapeutic dependency on LZK and that small-molecule inhibition of its catalytic function decreased the viability of ESCC cells with amplified MAP3K13. Inhibition of LZK suppressed tumor growth in MAP3K13-amplified ESCC patient-derived xenograft mice treated orally with a newly described LZK inhibitor. We discovered that LZK is required to sustain AKT activation in ESCC and head and neck squamous cell carcinoma (HNSCC), in which depletion, degradation, or treatment with the LZK inhibitor GNE-3511 or an improved inhibitor suppressed AKT activation. AKT activation could be rescued by the expression of an LZK drug-resistant mutant, indicating that suppression was specific to LZK. AKT and LZK co-localized and interacted in cells, and LZK enhanced AKT phosphorylation at S473 and T450 in vitro. This pattern of AKT phosphorylation reflected a noncatalytic scaffold function of LZK as LZK inhibitors did not suppress AKT activation and a kinase-dead LZK mutant promoted AKT activation. AKT inhibitors reduced LZK-induced activation of AKT, indicating that LZK facilitates AKT autophosphorylation. Furthermore, GNE-3511 inhibited the interaction of LZK with AKT in coimmunoprecipitation experiments. Molecular modeling supported a mechanism whereby LZK binds and dislodges AKT’s pleckstrin homology domain to promote AKT autophosphorylation. Our findings demonstrate that MAP3K13-amplified tumors are dependent on LZK-mediated AKT scaffolding, supporting LZK inhibition as a therapeutic strategy in ESCC and HNSCC. Statement of significance: LZK promotes AKT autophosphorylation and tumor growth in ESCC and HNSCC; its inhibition suppresses AKT activation and viability, suggesting a novel therapeutic strategy for these cancers.
- 3 November 2026
- Published by American Association for Cancer Research (AACR)
Open AccessData from Suppression of AKT Activation through LZK Inhibition Limits Tumor Growth in Esophageal and Head and Neck Cancers
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers worldwide due to its aggressive nature and lack of knowledge of underlying oncogenic drivers, limiting treatment options. Approximately 60% of ESCC cases have amplification/overexpression of MAP3K13, which encodes the kinase LZK. In this study, we found that MAP3K13-amplified ESCC exhibits therapeutic dependency on LZK and that small-molecule inhibition of its catalytic function decreased the viability of ESCC cells with amplified MAP3K13. Inhibition of LZK suppressed tumor growth in MAP3K13-amplified ESCC patient-derived xenograft mice treated orally with a newly described LZK inhibitor. We discovered that LZK is required to sustain AKT activation in ESCC and head and neck squamous cell carcinoma (HNSCC), in which depletion, degradation, or treatment with the LZK inhibitor GNE-3511 or an improved inhibitor suppressed AKT activation. AKT activation could be rescued by the expression of an LZK drug-resistant mutant, indicating that suppression was specific to LZK. AKT and LZK co-localized and interacted in cells, and LZK enhanced AKT phosphorylation at S473 and T450 in vitro. This pattern of AKT phosphorylation reflected a noncatalytic scaffold function of LZK as LZK inhibitors did not suppress AKT activation and a kinase-dead LZK mutant promoted AKT activation. AKT inhibitors reduced LZK-induced activation of AKT, indicating that LZK facilitates AKT autophosphorylation. Furthermore, GNE-3511 inhibited the interaction of LZK with AKT in coimmunoprecipitation experiments. Molecular modeling supported a mechanism whereby LZK binds and dislodges AKT’s pleckstrin homology domain to promote AKT autophosphorylation. Our findings demonstrate that MAP3K13-amplified tumors are dependent on LZK-mediated AKT scaffolding, supporting LZK inhibition as a therapeutic strategy in ESCC and HNSCC. Statement of significance: LZK promotes AKT autophosphorylation and tumor growth in ESCC and HNSCC; its inhibition suppresses AKT activation and viability, suggesting a novel therapeutic strategy for these cancers.
- Open Access
- 3 November 2026
- Published by American Association for Cancer Research (AACR)
Related Manuscript File from Suppression of AKT Activation through LZK Inhibition Limits Tumor Growth in Esophageal and Head and Neck Cancers
Related Manuscript File from Suppression of AKT Activation through LZK Inhibition Limits Tumor Growth in Esophageal and Head and Neck Cancers
- 3 November 2026
- Published by American Association for Cancer Research (AACR)
Open AccessRelated Manuscript File from Suppression of AKT Activation through LZK Inhibition Limits Tumor Growth in Esophageal and Head and Neck Cancers
Related Manuscript File from Suppression of AKT Activation through LZK Inhibition Limits Tumor Growth in Esophageal and Head and Neck Cancers