Ubiquitin Mediated Degradation of EGFR by 17 β-estradiol in Triple
Negative MDA-MB-231 (TNBC) Breast Cancer Cells Line

Khode, Vitthal; Patil, Sumangala; Kaveeshwar, Vishwas; Ruikar, Komal; Bargale, Anil; Sarathkumar, E.; Patil, Satish G

doi:10.2174/1566524021666210729144713

Cited by 4 publications

(5 citation statements)

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“…Additionally, fluorescently labelled PEG-NEs were formulated as a negative control. The cell lines used to perform this experiment were MCF-7 and MDA-MB-231, as we have observed in previous works [ 36 , 37 ] and in our group that MDA-MB-231 expresses EGFR and MCF-7 expresses EpCAM. Additionally, to confirm this protein expression, we performed immunohistochemical analysis on both cell lines ( Figure 6 A).…”

Section: Resultsmentioning

confidence: 99%

Peptide-Functionalized Nanoemulsions as a Promising Tool for Isolation and Ex Vivo Culture of Circulating Tumor Cells

et al. 2022

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Circulating Tumor Cells (CTCs) are shed from primary tumors and travel through the blood, generating metastases. CTCs represents a useful tool to understand the biology of metastasis in cancer disease. However, there is a lack of standardized protocols to isolate and culture them. In our previous work, we presented oil-in-water nanoemulsions (NEs) composed of lipids and fatty acids, which showed a benefit in supporting CTC cultures from metastatic breast cancer patients. Here, we present Peptide-Functionalized Nanoemulsions (Pept-NEs), with the aim of using them as a tool for CTC isolation and culture in situ. Therefore, NEs from our previous work were surface-decorated with the peptides Pep10 and GE11, which act as ligands towards the specific cell membrane proteins EpCAM and EGFR, respectively. We selected the best surface to deposit a layer of these Pept-NEs through a Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D) method. Next, we validated the specific recognition of Pept-NEs for their protein targets EpCAM and EGFR by QCM-D and fluorescence microscopy. Finally, a layer of Pept-NEs was deposited in a culture well-plate, and cells were cultured on for 9 days in order to confirm the feasibility of the Pept-NEs as a cell growth support. This work presents peptide-functionalized nanoemulsions as a basis for the development of devices for the isolation and culture of CTCs in situ due to their ability to specifically interact with membrane proteins expressed in CTCs, and because cells are capable of growing on top of them.

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Section: Resultsmentioning

confidence: 99%

Peptide-Functionalized Nanoemulsions as a Promising Tool for Isolation and Ex Vivo Culture of Circulating Tumor Cells

et al. 2022

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“…Studies demonstrated that estrogens can exert functions by nonclassical ER mechanism. It has been reported that MDA‐MB‐231 cells can still be affected by estrogens even if ER is negative 45 . So far, the NK cell‐related mechanism for this abnormal low miR‐338‐3p level in BC cells is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that MDA-MB-231 cells can still be affected by estrogens even if ER is negative. 45 So far, the NK cellrelated mechanism for this abnormal low miR-338-3p level in BC cells is not clear. Therefore, we tend to explore the relationships of miRNA and BC.…”

Section: Discussionmentioning

confidence: 99%

The estrogen/miR‐338‐3p/ADAM17 axis enhances the viability of breast cancer cells via suppressing NK cell's function

Shi

Pan

Chen

et al. 2023

Environmental Toxicology

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Natural killer (NK) cells are the critical elements of the innate immune response and implicated in rapidly recognizing and eliminating cancer cells. However, the tumorsuppressive ability of NK cells is often impaired in several cancer types. The critical roles of microRNAs have been elucidated by increasing evidences, while the regulation of miR-338-3p in anti-tumor activation of NK cells and its relationship with estrogen in breast cancer (BC) are still confusing. Here, miR-338-3p level was found to be significantly downregulated in BC tissues and estrogen receptor positive (ER + ) cells, this difference was more obvious in ER + patients or BC patients at advanced stage (TNM III and IV). MiR-338-3p level was shown to be downregulated by 17β-estradiol in BC cells (MDA-MB-231 cells and MCF-7) in vitro. MiR-338-3p overexpression decreased disintegrin and metalloprotease-17 (ADAM17) secretion in MDA-MB-231 (ER À ) and MCF-7 (ER + ) cells. In addition, miR-338-3p overexpression or treatment with anti-ADAM17 antibody could down-regulate granzyme B, CD16, and NKG2D in NK cells, which was reversed by human recombinant ADAM17. Furthermore, these educated NK cells could promote the viability of MDA-MB-231 or MCF-7 cells. Taken together, our results demonstrate that miR-338-3p was negatively regulated by estrogen in BC cells, impairing NK cell's activity by the upregulation of ADAM17, and conversely promoted the viability of BC cells. Therefore, the estrogen/miR-338-3p/ADAM17 axis is critically implicated in BC pathogenesis and may provide potential targets for BC diagnosis and treatment.

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“…Other possible mechanisms that explain why estradiol benzoate and 17β-estradiol decrease HBx and inhibit HBV viral activity are also needed to be investigated. Estradiol may mediate its anti-HBV function through the Estrogen receptor-α (ER-α) signaling pathway as it does in HIV replication [ 22 ], or through activation of the E3 ubiquitination pathway by estradiol benzoate which may contribute to a decrease in HBV-related protein [ 23 ]. A distribution and a significant decrease in NTCP were observed in EB-induced cholestatic rats, as previously reported [ 24 ], which is the primary receptor of the HBV entrance of cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of Estradiol Benzoate as an Inhibitor of HBx Using Inducible Stably Transfected HepG2 Cells Expressing HiBiT Tagged HBx

Chen

et al. 2022

Molecules

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HBx plays a significant role in the cccDNA epigenetic modification regulating the hepatitis B virus (HBV) life cycle and in hepatocyte proliferation and carcinogenesis. By using the sleeping-beauty transposon system, we constructed a tetracycline-induced HBx-expressing stable cell line, SBHX21. HBx with a HiBiT tag can be quickly detected utilizing a NanoLuc-based HiBiT detection system. By screening a drug library using SBHX21 cells, we identified estradiol benzoate as a novel anti-HBx agent. Estradiol benzoate also markedly reduced the production of HBeAg, HBsAg, HBV pgRNA, and HBV DNA in a dose-dependent manner, suggesting that estradiol benzoate could be an anti-HBV agent. Docking model results revealed that estradiol benzoate binds to HBx at TRP87 and TRP107. Collectively, our results suggest that estradiol benzoate inhibits the HBx protein and HBV transcription and replication, which may serve as a novel anti-HBV molecular compound for investigating new treatment strategies for HBV infection.

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Ubiquitin Mediated Degradation of EGFR by 17 β-estradiol in Triple Negative MDA-MB-231 (TNBC) Breast Cancer Cells Line

Cited by 4 publications

References 0 publications

Peptide-Functionalized Nanoemulsions as a Promising Tool for Isolation and Ex Vivo Culture of Circulating Tumor Cells

Peptide-Functionalized Nanoemulsions as a Promising Tool for Isolation and Ex Vivo Culture of Circulating Tumor Cells

The estrogen/miR‐338‐3p/ADAM17 axis enhances the viability of breast cancer cells via suppressing NK cell's function

Identification of Estradiol Benzoate as an Inhibitor of HBx Using Inducible Stably Transfected HepG2 Cells Expressing HiBiT Tagged HBx

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