Therapeutic aspects of AMPK in breast cancer: Progress, challenges, and future directions

Ponnusamy, Lavanya; Natarajan, Sathan Raj; Thangaraj, Karthik; Manoharan, Ravi

doi:10.1016/j.bbcan.2020.188379

Cited by 40 publications

(28 citation statements)

References 121 publications

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“…Breast cancer (BC) is the most frequently diagnosed malignancy and the major cause of cancer-related death in females worldwide [1]. The reason is that BC is confronted with high invasion, metastasis and recurrence rate, especially the metastatic capacity to the brain and lungs [2]. Adipose tissue plays a crucial role as an energy storage depot and can act as endocrine cells to produce various bioactive substances [3].…”

Section: Introductionmentioning

confidence: 99%

Cancer-associated adipocytes: emerging supporters in breast cancer

Zhao

Zeng

et al. 2020

J Exp Clin Cancer Res

120

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Breast cancer (BC) is a malignant breast tumor confronted with high invasion, metastasis and recurrence rate, and adipocytes are the largest components in breast tissue. The aberrant adipocytes, especially the BC-neighbored cancer-associated adipocytes (CAAs), are found in the invasive front of BC. CAAs present a vicious phenotype compared with mature mammary adipocytes and mediate the crosstalk network between adipocytes and BC cells. By releasing multiple adipokines such as leptin, adiponectin, interleukin (IL)-6, chemokine ligand 2 (CCL2) and chemokine ligand 5 (CCL5), CAAs play essential roles in favor of proliferation, angiogenesis, dissemination, invasion and metastasis of BC. This article reviews the recent existing CAAs studies on the functions and mechanisms of adipocytes in the development of BC, including adipokine regulating, metabolic reprogramming, extracellular matrix (ECM) remodeling, microRNAs (miRNAs) and immune cell adjusting. Besides, adipocyte secretome and cellular interactions are implicated in the intervention to BC therapy and autologous fat grafting of breast reconstruction. Therefore, the potential functions and mechanisms of CAAs are very important for unveiling BC oncogenesis and progress. Deciphering the complex network between CAAs and BC is critical for designing therapeutic strategies and achieving the maximum therapeutic effects of BC.

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Section: Introductionmentioning

confidence: 99%

Cancer-associated adipocytes: emerging supporters in breast cancer

Zhao

Zeng

et al. 2020

J Exp Clin Cancer Res

120

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“…KEGG pathways analysis demonstrated that the DEGs were mainly enriched in cell cycle, AMPK signaling pathway and pathways in cancer, which are potentially associated in the progression of breast tumor and used as the regulating target for cancer treatment [19,20]. For instance, downregulation of AMPK activity or decreased expression appear to promote breast tumorigenesis, while AMPK activation was found to impede tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Astragalus Polysaccharide Regulates EGFR and ANXA1 Expression to Inhibit Tumor Growth

Li¹,

Hu²,

Li³

et al. 2021

Preprint

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Background: Astragalus polysaccharide (APS) has been frequently used as an adjuvant agent responsible for its immunoregulatory activity to enhance efficacy and reduce toxicity of chemotherapy used in the management of breast cancer. However, the other synergism mechanism of APS remains unclear. Methods: The expression profiles of breast cancer biological data (E-GEOD-10780), (E-GEOD-65194), (E-GEOD-10810), (E-GEOD-42568), (E-GEOD-61304), (E-GEOD-7904) and (E-GEOD-15852) were retrieved from European bioinformatics institute (EBI) database to identify differentially expressed genes (DEGs). Gene Ontology and pathway enrichment analyses were carried out. The protein–protein interaction (PPI) networks of the DEGs were constructed by STRING online database. Finally, STRING was applied to construct the PPI networks of the DEGs associated with cell proliferation, cell cycle and cell apoptosis from GO enrichment analysis. Subsequently, hub and common genes that might be the potential targets and possible mechanism behind APS in vivo direct anti-tumor activity on breast cancer were identified. Meanwhile, we evaluated the mRNA and protein expression levels of these key targets using multiple biological analyses.Results: In total, 116 down-regulated and 73 up-regulated differential expressed genes (DEGs) were examined from seven gene expression datasets. Top ten hub genes were obtained in four typical protein-protein interaction (PPI) network of DEGs involved in each specific biological process (BP, cell cycle, cell proliferation, cell apoptosis and death) that was related to inhibitory activity of APS in vitro against breast cancer cell lines. Four common DEGs (EGFR, ANXA1, KIF14 and IGF1) were further identified in the above four BP-PPI networks, among which EGFR and ANXA1 were the hub genes that were potentially linked to the progression of breast cancer. The results of biological detections indicated that APS could down-regulated EGFR and up-regulated ANXA1 expression.Conclusion: In conclusion, the present study may provide potential molecular therapeutic targets and a new insight into the mechanism of APS against breast cancer.

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“…It is known that AKR1C3 is abundantly expressed in BC and is associated with a worse prognosis. AKR1C3 is also related to DOX resistance in human BC (2). Byrns et al confirmed that the expression of AKR1C3 in MCF-7 cells resulted in the elevated ratio of 17b-estradiol: progesterone, conferring a proliferative preponderance to BC cells (3).…”

Section: Chemotherapymentioning

confidence: 98%

“…Breast cancer (BC) is ranked as the most common malignancy and the major leading cause of cancer-related death among women worldwide ( 1 ). The main reason is that advanced BC is frequently confronted with a high rate of relapse, invasion, and metastasis, especially the organotropic metastasis capacity to the brain and lung ( 2 ). Obesity is a pivotal lifestyle driver of the current and prospective BC rates.…”

Section: Introductionmentioning

confidence: 99%

Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

Zhao

et al. 2021

Front. Oncol.

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Obesity is defined as a chronic disease induced by an imbalance of energy homeostasis. Obesity is a widespread health problem with increasing prevalence worldwide. Breast cancer (BC) has already been the most common cancer and one of the leading causes of cancer death in women worldwide. Nowadays, the impact of the rising prevalence of obesity has been recognized as a nonnegligible issue for BC development, outcome, and management. Adipokines, insulin and insulin-like growth factor, sex hormone and the chronic inflammation state play critical roles in the vicious crosstalk between obesity and BC. Furthermore, obesity can affect the efficacy and side effects of multiple therapies such as surgery, radiotherapy, chemotherapy, endocrine therapy, immunotherapy and weight management of BC. In this review, we focus on the current landscape of the mechanisms of obesity in fueling BC and the impact of obesity on diverse therapeutic interventions. An in-depth exploration of the underlying mechanisms linking obesity and BC will improve the efficiency of the existing treatments and even provide novel treatment strategies for BC treatment.

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Therapeutic aspects of AMPK in breast cancer: Progress, challenges, and future directions

Cited by 40 publications

References 121 publications

Cancer-associated adipocytes: emerging supporters in breast cancer

Cancer-associated adipocytes: emerging supporters in breast cancer

Astragalus Polysaccharide Regulates EGFR and ANXA1 Expression to Inhibit Tumor Growth

Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

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