The Multifaceted Functions of Autophagy in Breast Cancer Development and Treatment

Niklaus, Nicolas J.; Tokarchuk, Igor; Zbinden, Mara; Schläfli, Anna M.; Maycotte, Paola; Tschan, Mario P.

doi:10.3390/cells10061447

Cited by 44 publications

(48 citation statements)

References 206 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Namely, autophagy is a pivotal process in control of cell fate and significantly correlates with apoptosis via inactivating the mammalian target of rapamycin (mTOR) signaling pathway or directly activates the initiation step of autophagy by phosphorylating unc-51-like autophagy activating kinase 1 (ULK1). In terms of cancer initiation, autophagy is considered tumor-suppressive due to its cytoprotective role (23,25,39,40). Notably, Marsh et al (25) discovered autophagy could inhibit the metastasis of BC cells by accumulating the autophagy cargo receptor (ACR), neighbor to BRCA1.…”

Section: Discussionmentioning

confidence: 99%

Identifying and Validating of an Autophagy-Related Gene Signature for the Prediction of Early Relapse in Breast Cancer

et al. 2022

View full text Add to dashboard Cite

BackgroundCompelling evidence has demonstrated the pivotal role of autophagy in the prognosis of breast cancer. Breast cancer (BC) patients with early relapse consistently exhibited worse survival.MethodsThe autophagy-related genes were derived from the Human Autophagy Database (HADb) and high-sequencing data were obtained from The Cancer Genome Atlas (TCGA). Discrepantly expressed autophagy genes (DEAGs) between early relapse and long-term survival groups were performed using the Linear Models for Microarray data (LIMMA) method. Lasso Cox regression analysis was conducted for the selection of the 4-gene autophagy-related gene signature. GSE42568 and GSE21653 databases were enrolled in this study for the external validation of the signature. Then patients were divided into high and low-risk groups based on the specific score formula. GSEA was used to discover the related signaling pathway. The Kaplan-Meier curves and the receiver operating characteristic (ROC) curves were used to evaluate the discrimination and accuracy of the 4-gene signature.ResultsA signature composed of four autophagy-related mRNA including APOL1, HSPA8, SIRT1, and TP73, was identified as significantly associated with the early relapse in BC patients. Time-dependent receiver-operating characteristic at 1 year suggested remarkable accuracy of the signature [area under the curve (AUC = 0.748)]. The risk score model based on the autophagy-related signature showed favorable predicting value in 1-, 2-, and 3-year relapse-free survival (RFS) in training and two validating cohorts. The GSEA displayed gene sets were remarkably enriched in carcinogenic activation pathways and autophagy-related pathways. The nomogram involving three variables (progesterone receptor status, T stage, and 4-gene signature) exhibited relatively good discrimination with a C-index of 0.766.ConclusionsOur study establishes an autophagy-related 4-gene signature that can effectively stratify the high-risk and low-risk BC patients for early relapse. Combined with the clinicopathological variables, the signature could significantly help oncologists tailor more efficient treatment strategies for BC patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Identifying and Validating of an Autophagy-Related Gene Signature for the Prediction of Early Relapse in Breast Cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The role of autophagy in cancer in general and in breast cancer in particular is emerging [ 43 , 44 , 45 ]. Regulation of autophagy is considered a method to prevent breast cancer and break therapeutic resistance (reviewed in [ 46 ]). It was shown that the vitamin D/VDR axis in breast cancer is regulated by many miRNAs [ 47 ].…”

Section: Vitamin D Signaling In Breast Cancermentioning

confidence: 99%

Vitamin D May Protect against Breast Cancer through the Regulation of Long Noncoding RNAs by VDR Signaling

Błasiak

Chojnacki

Pawłowska

et al. 2022

IJMS

View full text Add to dashboard Cite

Dietary vitamin D3 has attracted wide interest as a natural compound for breast cancer prevention and therapy, supported by in vitro and animal studies. The exact mechanism of such action of vitamin D3 is unknown and may include several independent or partly dependent pathways. The active metabolite of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D, calcitriol), binds to the vitamin D receptor (VDR) and induces its translocation to the nucleus, where it transactivates a myriad of genes. Vitamin D3 is involved in the maintenance of a normal epigenetic profile whose disturbance may contribute to breast cancer. In general, the protective effect of vitamin D3 against breast cancer is underlined by inhibition of proliferation and migration, stimulation of differentiation and apoptosis, and inhibition of epithelial/mesenchymal transition in breast cells. Vitamin D3 may also inhibit the transformation of normal mammary progenitors into breast cancer stem cells that initiate and sustain the growth of breast tumors. As long noncoding RNAs (lncRNAs) play an important role in breast cancer pathogenesis, and the specific mechanisms underlying this role are poorly understood, we provided several arguments that vitamin D3/VDR may induce protective effects in breast cancer through modulation of lncRNAs that are important for breast cancer pathogenesis. The main lncRNAs candidates to mediate the protective effect of vitamin D3 in breast cancer are lncBCAS1-4_1, AFAP1 antisense RNA 1 (AFAP1-AS1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), long intergenic non-protein-coding RNA 511 (LINC00511), LINC00346, small nucleolar RNA host gene 6 (SNHG6), and SNHG16, but there is a rationale to explore several other lncRNAs.

show abstract

“…BC is immensely heterogeneous with diverse histopathological properties and molecular profiles. From a molecular viewpoint, 4 distinct BC subtypes have been identified including luminal A, luminal B, human epidermal growth factor receptor 2 positive (HER2+), and triple-negative [4,5]. In addition, BC can be categorised into immunohistological subtypes based on oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status.…”

Section: The Molecular Characteristics Of Dormant Breast Cancer Cellsmentioning

confidence: 99%

Dormancy in Breast Cancer, the Role of Autophagy, lncRNAs, miRNAs and Exosomes

Jahangiri

2022

IJMS

View full text Add to dashboard Cite

Breast cancer (BC) is the most frequently diagnosed cancer in women for which numerous diagnostic and therapeutic options have been developed. Namely, the targeted treatment of BC, for the most part, relies on the expression of growth factors and hormone receptors by these cancer cells. Despite this, close to 30% of BC patients may experience relapse due to the presence of minimal residual disease (MRD) consisting of surviving disseminated tumour cells (DTCs) from the primary tumour which can colonise a secondary site. This can lead to either detectable metastasis or DTCs entering a dormant state for a prolonged period where they are undetectable. In the latter, cells can re-emerge from their dormant state due to intrinsic and microenvironmental cues leading to relapse and metastatic outgrowth. Pre- and clinical studies propose that targeting dormant DTCs may inhibit metastasis, but the choice between keeping them dormant or forcing their “awakening” is still controversial. This review will focus on cancer cells’ microenvironmental cues and metabolic and molecular properties, which lead to dormancy, relapse, and metastatic latency in BC. Furthermore, we will focus on the role of autophagy, long non-coding RNAs (lncRNAs), miRNAs, and exosomes in influencing the induction of dormancy and awakening of dormant BC cells. In addition, we have analysed BC treatment from a viewpoint of autophagy, lncRNAs, miRNAs, and exosomes. We propose the targeted modulation of these processes and molecules as modern aspects of precision medicine for BC treatment, improving both novel and traditional BC treatment options. Understanding these pathways and processes may ultimately improve BC patient prognosis, patient survival, and treatment response.

show abstract

The Multifaceted Functions of Autophagy in Breast Cancer Development and Treatment

Cited by 44 publications

References 206 publications

Identifying and Validating of an Autophagy-Related Gene Signature for the Prediction of Early Relapse in Breast Cancer

Identifying and Validating of an Autophagy-Related Gene Signature for the Prediction of Early Relapse in Breast Cancer

Vitamin D May Protect against Breast Cancer through the Regulation of Long Noncoding RNAs by VDR Signaling

Dormancy in Breast Cancer, the Role of Autophagy, lncRNAs, miRNAs and Exosomes

Contact Info

Product

Resources

About