Biglycan Promotes Cancer Stem Cell Properties, NFκB Signaling and Metastatic Potential in Breast Cancer Cells

Cancers

Ritama Paul¹  Michael Haas¹  Jun-Lin Guan¹  Kanakaraju Manupati¹  Syn Kok Yeo¹  Mingang Hao¹  Zhaoqun Christine Bian²  Tammy M. Holm² 

[1] Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA;Department of Surgery, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267, USA;

关键词: breast cancer stem cells;    biglycan;    metastasis;    NFκB pathway;    luminal breast cancer;   

DOI  :  10.3390/cancers14020455

来源: DOAJ

【 摘 要 】

It is a major challenge to treat metastasis due to the presence of heterogenous BCSCs. Therefore, it is important to identify new molecular targets and their underlying molecular mechanisms in various BCSCs to improve treatment of breast cancer metastasis. Here, we performed RNA sequencing on two distinct co-existing BCSC populations, ALDH⁺ and CD29^hi CD61⁺ from PyMT mammary tumor cells and detected upregulation of biglycan (BGN) in these BCSCs. Genetic depletion of BGN reduced BCSC proportions and tumorsphere formation. Furthermore, BCSC associated aggressive traits such as migration and invasion were significantly reduced by depletion of BGN. Glycolytic and mitochondrial metabolic assays also revealed that BCSCs exhibited decreased metabolism upon loss of BGN. BCSCs showed decreased activation of the NFκB transcription factor, p65, and phospho-IκB levels upon BGN ablation, indicating regulation of NFκB pathway by BGN. To further support our data, we also characterized CD24⁻/CD44⁺ BCSCs from human luminal MCF-7 breast cancer cells. These CD24⁻/CD44⁺ BCSCs similarly exhibited reduced tumorigenic phenotypes, metabolism and attenuation of NFκB pathway after knockdown of BGN. Finally, loss of BGN in ALDH⁺ and CD29^hi CD61⁺ BCSCs showed decreased metastatic potential, suggesting BGN serves as an important therapeutic target in BCSCs for treating metastasis of breast cancer.

【 授权许可】

Unknown