Work

CIDEC impairs mitochondrial fitness and blocks protective autophagy via the inhibition of cGMP/PKG pathway to exert tumor-suppressive effects in breast cancer

Year: 2026

Type: article

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.

Source: Cellular Oncology

DOI: 10.1007/s13402-026-01211-8

Authors: Xuchu Jin, Yu Liu, Xinyu Zheng, Yangke He

Institutions: University of Electronic Science and Technology of China, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, First Hospital of China Medical University, China Medical University

Language: English

Topic: Autophagy in Disease and Therapy

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $4,390