AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer

Li, Yang; She, Wenyan; Xu, Xiaoran; Liu, Yixin; Wang, Xinyu; Tian, Sheng; Li, Shiyi; Wang, Miao; Yu, Chuan; Liu, Pan; Huang, Tianhe; Wei, Yongchang

doi:10.1631/jzus.b2200351

Cited by 2 publications

(1 citation statement)

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“…Within the field of gastric cancer therapy, targeting strategies against mitochondria have shown significant clinical potential. For example, by targeting pyruvate dehydrogenase kinase 1 (PDK1), the PI3K/AKT/mTOR signaling pathway can be effectively inhibited, thereby inducing mitochondria-dependent apoptotic mechanisms and providing a new strategy for gastric cancer treatment [ 12 ]. Some researchers have also revealed how downregulation of NDUFS1, the largest subunit of ubiquinone oxidoreductase (complex 1) in the mitochondrial electron transport chain, promotes malignant progression of gastric cancer by activating the mROS-HIF1α-FBLN5 signaling pathway, emphasizing the critical role of targeting the mitochondrial components in gastric cancer therapy [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Integrated multi-omics analysis and machine learning developed a prognostic model based on mitochondrial function in a large multicenter cohort for Gastric Cancer

Ma,

Jin,

Xue

et al. 2024

J Transl Med

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Background Gastric cancer (GC) is a common and aggressive type of cancer worldwide. Despite recent advancements in its treatment, the prognosis for patients with GC remains poor. Understanding the mechanisms of cell death in GC, particularly those related to mitochondrial function, is crucial for its development and progression. However, more research is needed to investigate the significance of the interaction between mitochondrial function and GC cell death. Methods We employed a robust computational framework to investigate the role of mitochondria-associated proteins in the progression of GC in a cohort of 1,199 GC patients. Ten machine learning algorithms were utilized and combined into 101 unique combinations. Ultimately, we developed a Mitochondrial-related-Score (MitoScore) using the machine learning model that exhibited the best performance. We observed the upregulation of LEMT2 and further explored its function in tumor progression. Mitochondrial functions were assessed by measuring mitochondrial ATP, mitochondrial membrane potential, and levels of lactate, pyruvate, and glucose. Results MitoScore showed significant correlations with GC immune and metabolic functions. The higher MitoScore subgroup exhibited enriched metabolic pathways and higher immune activity. Overexpression of LETM2 (leucine zipper and EF-hand containing transmembrane protein 2) significantly enhanced tumor proliferation and metastasis. LETM2 plays a role in promoting GC cell proliferation by activating the mTOR pathway, maintaining mitochondrial homeostasis, and promoting glycolysis. Conclusion The powerful machine learning framework highlights the significant potential of MitoScore in providing valuable insights and accurate assessments for individuals with GC. This study also enhances our understanding of LETM2 as an oncogene signature in GC. LETM2 may promote tumor progression by maintaining mitochondrial health and activating glycolysis, offering potential targets for diagnosis, treatment, and prognosis of GC.

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Section: Introductionmentioning

confidence: 99%