Autophagy and Breast Cancer: Connected in Growth, Progression, and Therapy

Wu, Qitong; Sharma, Dipali

doi:10.3390/cells12081156

Cited by 28 publications

(8 citation statements)

References 297 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Autophagy has been reported to be closely correlated with the malignant transformation of cancer cells (Onorati et al 2018 ; Li et al 2020 ). Existing study has demonstrated that autophagy may play the multifaceted role in breast cancer tumorigenesis and metastasis (Wu and Sharma 2023 ; Niklaus, et al 2021 ). Notably, PDK4 regulates autophagy to participate in vascular calcification (Ma et al 2020 ) and non-small cell lung cancer (Zhang et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Abrogating PDK4 activates autophagy-dependent ferroptosis in breast cancer via ASK1/JNK pathway

Shi,

Wang,

Chen

et al. 2024

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Background Targeting ferroptosis mediated by autophagy presents a novel therapeutic approach to breast cancer, a mortal neoplasm on the global scale. Pyruvate dehydrogenase kinase isozyme 4 (PDK4) has been denoted as a determinant of breast cancer metabolism. The target of this study was to untangle the functional mechanism of PDK4 in ferroptosis dependent on autophagy in breast cancer. Methods RT-qPCR and western blotting examined PDK4 mRNA and protein levels in breast cancer cells. Immunofluorescence staining appraised light chain 3 (LC3) expression. Fe (2 +) assay estimated total iron level. Relevant assay kits and C11-BODIPY (591/581) staining evaluated lipid peroxidation level. DCFH-DA staining assayed intracellular reactive oxygen species (ROS) content. Western blotting analyzed the protein levels of autophagy, ferroptosis and apoptosis-signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) pathway-associated proteins. Results PDK4 was highly expressed in breast cancer cells. Knockdown of PDK4 induced the autophagy of breast cancer cells and 3-methyladenine (3-MA), an autophagy inhibitor, countervailed the promoting role of PDK4 interference in ferroptosis in breast cancer cells. Furthermore, PDK4 knockdown activated ASK1/JNK pathway and ASK1 inhibitor (GS-4997) partially abrogated the impacts of PDK4 absence on the autophagy and ferroptosis in breast cancer cells. Conclusion To sum up, deficiency of PDK4 activated ASK1/JNK pathway to stimulate autophagy-dependent ferroptosis in breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Abrogating PDK4 activates autophagy-dependent ferroptosis in breast cancer via ASK1/JNK pathway

Shi,

Wang,

Chen

et al. 2024

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

show abstract

“…ACD in response to anticancer drugs has been reported, for example, in breast, colon, and ovarian cancer tissues [ 67 , 68 ]. Tamoxifen induces ACD in breast cancer cells in association with Akt downregulation; conversely, autophagy is involved in tamoxifen resistance via the activation of the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway [ 69 ]. Histone deacetylase inhibitors induce mitochondria-mediated apoptosis and caspase-independent ACD in multiple human cancer cell types [ 70 ].…”

Section: Non-apoptotic Cell Deathmentioning

confidence: 99%

Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy

Kim,

Kin,

Beck

2024

Cancers

View full text Add to dashboard Cite

Anticancer drugs induce apoptotic and non-apoptotic cell death in various cancer types. The signaling pathways for anticancer drug-induced apoptotic cell death have been shown to differ between drug-sensitive and drug-resistant cells. In atypical multidrug-resistant leukemia cells, the c-Jun/activator protein 1 (AP-1)/p53 signaling pathway leading to apoptotic death is altered. Cancer cells treated with anticancer drugs undergo c-Jun/AP-1–mediated apoptotic death and are involved in c-Jun N-terminal kinase activation and growth arrest- and DNA damage-inducible gene 153 (Gadd153)/CCAAT/enhancer-binding protein homologous protein pathway induction, regardless of the p53 genotype. Gadd153 induction is associated with mitochondrial membrane permeabilization after anticancer drug treatment and involves a coupled endoplasmic reticulum stress response. The induction of apoptosis by anticancer drugs is mediated by the intrinsic pathway (cytochrome c, Cyt c) and subsequent activation of the caspase cascade via proapoptotic genes (e.g., Bax and Bcl-xS) and their interactions. Anticancer drug-induced apoptosis involves caspase-dependent and caspase-independent pathways and occurs via intrinsic and extrinsic pathways. The targeting of antiapoptotic genes such as Bcl-2 enhances anticancer drug efficacy. The modulation of apoptotic signaling by Bcl-xS transduction increases the sensitivity of multidrug resistance-related protein-overexpressing epidermoid carcinoma cells to anticancer drugs. The significance of autophagy in cancer therapy remains to be elucidated. In this review, we summarize current knowledge of cancer cell death-related signaling pathways and their alterations during anticancer drug treatment and discuss potential strategies to enhance treatment efficacy.

show abstract

“…Current research suggests that autophagy can serve as a form of nutritional support for cellular self-repair. However, it may also contribute to tumor dormancy in breast cancer, potentially promoting chemoresistance and relapse ( 146 , 147 ).…”

Section: Other Forms Of Cell Death and Breast Cancermentioning

confidence: 99%

Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review)

Ai,

Yi,

Qiu

et al. 2024

Int J Oncol

View full text Add to dashboard Cite

Breast cancer arises from the malignant transformation of mammary epithelial cells under the influence of various carcinogenic factors, leading to a gradual increase in its prevalence. This disease has become the leading cause of mortality among female malignancies, posing a significant threat to the health of women. The timely identification of breast cancer remains challenging, often resulting in diagnosis at the advanced stages of the disease. Conventional therapeutic approaches, such as surgical excision, chemotherapy and radiotherapy, exhibit limited efficacy in controlling the progression and metastasis of the disease. Regulated cell death (RCD), a process essential for physiological tissue cell renewal, occurs within the body independently of external influences. In the context of cancer, research on RCD primarily focuses on cuproptosis, ferroptosis and pyroptosis. Mounting evidence suggests a marked association between these specific forms of RCD, and the onset and progression of breast cancer. For example, a cuproptosis vector can effectively bind copper ions to induce cuproptosis in breast cancer cells, thereby hindering their proliferation. Additionally, the expression of ferroptosis-related genes can enhance the sensitivity of breast cancer cells to chemotherapy. Likewise, pyroptosis-related proteins not only participate in pyroptosis, but also regulate the tumor microenvironment, ultimately leading to the death of breast cancer cells. The present review discusses the unique regulatory mechanisms of cuproptosis, ferroptosis and pyroptosis in breast cancer, and the mechanisms through which they are affected by conventional cancer drugs. Furthermore, it provides a comprehensive overview of the significance of these forms of RCD in modulating the efficacy of chemotherapy and highlights their shared characteristics. This knowledge may provide novel avenues for both clinical interventions and fundamental research in the context of breast cancer.

show abstract

Autophagy and Breast Cancer: Connected in Growth, Progression, and Therapy

Cited by 28 publications

References 297 publications

Abrogating PDK4 activates autophagy-dependent ferroptosis in breast cancer via ASK1/JNK pathway

Abrogating PDK4 activates autophagy-dependent ferroptosis in breast cancer via ASK1/JNK pathway

Impact of Complex Apoptotic Signaling Pathways on Cancer Cell Sensitivity to Therapy

Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review)

Contact Info

Product

Resources

About