CIDEC impairs mitochondrial fitness and blocks protective autophagy via the inhibition of cGMP/PKG pathway to exert tumor-suppressive effects in breast cancer.
[OBJECTIVE] Breast cancer continues to be a major contributor to cancer-associated deaths among the female population globally.
APA
Jin X, Liu Y, et al. (2026). CIDEC impairs mitochondrial fitness and blocks protective autophagy via the inhibition of cGMP/PKG pathway to exert tumor-suppressive effects in breast cancer.. Cellular oncology (Dordrecht, Netherlands), 49(3). https://doi.org/10.1007/s13402-026-01211-8
MLA
Jin X, et al.. "CIDEC impairs mitochondrial fitness and blocks protective autophagy via the inhibition of cGMP/PKG pathway to exert tumor-suppressive effects in breast cancer.." Cellular oncology (Dordrecht, Netherlands), vol. 49, no. 3, 2026.
PMID
42010152
Abstract
[OBJECTIVE] Breast cancer continues to be a major contributor to cancer-associated deaths among the female population globally. This study aims to investigate the functional role, underlying mechanisms, and clinical relevance of Cell death-inducing DFFA-like effector C (CIDEC) in breast cancer pathogenesis.
[METHODS] Integrated bioinformatics analysis of three gene expression datasets identified hub genes via protein-protein interaction network and multiple machine learning algorithms. The tumor-suppressive effects of CIDEC were evaluated in vitro using breast cancer cell lines by assessing viability, proliferation, migration, invasion, and apoptosis, and in vivo via a xenograft model. Mitochondrial function, autophagy, and the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathway were assessed using a pathway agonist and an autophagy inhibitor.
[RESULTS] A marked reduction in CIDEC expression was observed in breast cancer tissues and cellular models. CIDEC effectively curtailed tumor progression by impeding proliferation, migration, and invasive capacity, coupled with the induction of apoptotic cell death. Mechanistically, CIDEC impaired mitochondrial fitness, characterized by reduced adenosine triphosphate (ATP) production, dissipated mitochondrial membrane potential, and elevated reactive oxygen species. Concurrently, CIDEC blocked protective autophagy. These effects were mediated through the suppression of the cGMP/PKG pathway. Activating this pathway with 8-Br-cGMP reversed the tumor-suppressive phenotypes and mitochondrial dysfunction induced by CIDEC, whereas inhibiting autophagy attenuated this rescue.
[CONCLUSION] Our findings demonstrate that CIDEC functions as a novel tumor suppressor in breast cancer by disrupting mitochondrial fitness and inhibiting protective autophagy via the cGMP/PKG pathway. The CIDEC-cGMP/PKG axis represents a promising therapeutic target for breast cancer intervention.
[CLINICAL TRIAL NUMBER] Not applicable.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s13402-026-01211-8.
[METHODS] Integrated bioinformatics analysis of three gene expression datasets identified hub genes via protein-protein interaction network and multiple machine learning algorithms. The tumor-suppressive effects of CIDEC were evaluated in vitro using breast cancer cell lines by assessing viability, proliferation, migration, invasion, and apoptosis, and in vivo via a xenograft model. Mitochondrial function, autophagy, and the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathway were assessed using a pathway agonist and an autophagy inhibitor.
[RESULTS] A marked reduction in CIDEC expression was observed in breast cancer tissues and cellular models. CIDEC effectively curtailed tumor progression by impeding proliferation, migration, and invasive capacity, coupled with the induction of apoptotic cell death. Mechanistically, CIDEC impaired mitochondrial fitness, characterized by reduced adenosine triphosphate (ATP) production, dissipated mitochondrial membrane potential, and elevated reactive oxygen species. Concurrently, CIDEC blocked protective autophagy. These effects were mediated through the suppression of the cGMP/PKG pathway. Activating this pathway with 8-Br-cGMP reversed the tumor-suppressive phenotypes and mitochondrial dysfunction induced by CIDEC, whereas inhibiting autophagy attenuated this rescue.
[CONCLUSION] Our findings demonstrate that CIDEC functions as a novel tumor suppressor in breast cancer by disrupting mitochondrial fitness and inhibiting protective autophagy via the cGMP/PKG pathway. The CIDEC-cGMP/PKG axis represents a promising therapeutic target for breast cancer intervention.
[CLINICAL TRIAL NUMBER] Not applicable.
[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s13402-026-01211-8.
같은 제1저자의 인용 많은 논문 (5)
- Combining network pharmacology and experimental validation to study the action and mechanism of brusatol against lung adenocarcinoma.
- HSF2-HSP110 axis supports genome stability via RNA polymerase II transcription and DNA repair.
- Interpretable machine learning model for predicting refeeding syndrome after colorectal cancer surgery.
- Incidence and associated factors of venous thromboembolism in patients with gastric cancer across treatment settings after diagnosis: a systematic review and meta-analysis.
- Immunophenotypic Characterization of Neoplastic T Follicular Helper Cells by Flow Cytometry.