Activation of CD44-Lipoprotein lipase axis in breast cancer stem cells promotes tumorigenesis

Marumudi, Kanakaraju; Yeeravalli, Ragini; Kaushik, Komal; Singh, Digvijay; Mehra, Bhupendra; Gangane, Nitin; Gupta, Anupama; Goswami, Kalyan; Das, Amitava

doi:10.1016/j.bbadis.2021.166228

Cited by 18 publications

(16 citation statements)

References 54 publications

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“…Backing a detrimental role of LPL protein in breast cancer is work by Manupati et al. [ 41 ], who showed the activation of the transmembrane glycoprotein CD44 with hyaluronic acid in CD24 − /CD44 + breast cancer stem cells upregulated LPL mRNA and LPL protein expression; the siRNA‐mediated knockdown of CD44 reduced LPL protein expression versus control cells with scrambled siRNA. The authors further showed in vitro that the pan‐ sn ‐1 lipase inhibitor tetrahydrolipstatin significantly inhibited hyaluronic acid‐induced increases in migration, invasion, and mammosphere formation in Matrigel cultures of the CD24 − /CD44 + breast cancer stem cells isolated from MDA‐MD‐231 cells.…”

Section: Resultsmentioning

confidence: 99%

The breast cancer microenvironment and lipoprotein lipase: Another negative notch for a beneficial enzyme?

et al. 2023

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The energy demand of breast cancers is in part met through the β‐oxidation of exogenous fatty acids. Fatty acids may also be used to aid in cell signaling and toward the construction of new membranes for rapidly proliferating tumor cells. A significant quantity of fatty acids comes from the hydrolysis of lipoprotein triacylglycerols and phospholipids by lipoprotein lipase (LPL). The lipid obtained via LPL in the breast tumor microenvironment may thus promote breast tumor growth and development. In this hypothesis article, we introduce LPL, provide a meta‐analysis of RNAseq data showing that LPL is associated with poor prognosis, and explain how LPL might play a role in breast cancer prognosis over time.

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Section: Resultsmentioning

confidence: 99%

The breast cancer microenvironment and lipoprotein lipase: Another negative notch for a beneficial enzyme?

et al. 2023

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“…These populations have been known to differ in their functions at molecular level and exhibit different phenotypes [ 27 ]. Therefore, specific cell surface markers have been used to investigate these populations for identification of new molecular targets to improve therapeutic strategies [ 8 ]. Currently, the CSC surface markers CD24, CD44, CD133 and ALDH have been widely used in breast cancer for the isolation of BCSCs [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…The floating cells were removed with a PBS wash and culture medium returned. At different time intervals images were captured for analysis of migration rate as described previously [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

“…Cells remaining on the top of the membrane were removed. Cells that invaded the lower chamber and attached to the plate surface were quantified by fixing with 4% PFA, staining with crystal violet and counting [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

“…BCSCs are a subpopulation of cells with distinct tumorigenic properties within a mammary tumor and they drive distant metastasis to the secondary organs [ 8 ]. BCSCs have been isolated by using specific cell surface markers, such as CD24, CD44, CD133, CD29, CD61 and ALDH1 from heterogeneous populations within tumors [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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

Marumudi

Paul

Hao

et al. 2022

Cancers

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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 CD29hi 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 CD29hi CD61+ BCSCs showed decreased metastatic potential, suggesting BGN serves as an important therapeutic target in BCSCs for treating metastasis of breast cancer.

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New hydrazide derivatives of N‐amino‐11‐azaartemisinin as promising epidermal growth factor receptor inhibitors for therapeutic development in triple‐negative breast cancer

Karnatak,

Yadav,

Rathi

et al. 2024

Archiv der Pharmazie

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Triple‐negative breast cancer (TNBC) treatments, such as DNA‐damaging agents like carboplatin, pose considerable human toxicity and may contribute to cancer relapse. Artemisinin derivatives offer a less toxic alternative; however, their specific role in TNBC management remains to be established. To address this gap, computational models were employed to design and evaluate artemisinin‐based prototypes as potential TNBC therapeutics, aiming to provide safer and more effective treatment options for this aggressive cancer subtype. Among the series of hydrazide derivatives of azaartemisinin (10a–l) reported herein, compound 10j emerged as the most promising, exhibiting notable cytotoxicity with IC50 values of 1.74 and 1.64 µM against MDA‐MB‐231 and MDA‐MB‐468 cells, respectively. The clinically useful drug doxorubicin provided IC50 values of 0.29 and 0.29 µM against MDA‐MB‐231 and MDA‐MB‐468 cells, while artemisinin provided IC50 values of 107.30 and 116.60 µM, respectively. Furthermore, putative interactions between the synthesized compounds and the epidermal growth factor receptor (EGFR) were identified using molecular docking studies, suggesting a possible mechanism for their anticancer effect. Additionally, to determine the thermodynamic parameters of the interactions between artemisinin, azaartemisinin, and biomolecules, isothermal titration calorimetry experiments were performed. The binding constant value on the order of 104 indicates a comparatively stronger binding affinity of azaartemisinin with human serum albumin (HSA) compared to artemisinin with HSA. These findings support the potential of azaartemisinin derivatives as promising EGFR inhibitors for therapeutic development in TNBC, offering a new avenue for less toxic and more effective cancer treatments.

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Activation of CD44-Lipoprotein lipase axis in breast cancer stem cells promotes tumorigenesis

Cited by 18 publications

References 54 publications

The breast cancer microenvironment and lipoprotein lipase: Another negative notch for a beneficial enzyme?

The breast cancer microenvironment and lipoprotein lipase: Another negative notch for a beneficial enzyme?

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

New hydrazide derivatives of N‐amino‐11‐azaartemisinin as promising epidermal growth factor receptor inhibitors for therapeutic development in triple‐negative breast cancer

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