A novel tumor suppressor ZBTB1 regulates tamoxifen resistance and aerobic glycolysis through suppressing HER2 expression in breast cancer Cell Biology

In this study, we found that ZBTB1 is down-regulated in breast cancer and this down-regulation is associated with poor outcome of breast cancer patients. ZBTB1 suppresses breast cancer cell proliferation and tumor growth. The majority of breast cancers are estrogen receptor (ER) positive and selective estrogen receptor modulators such as tamoxifen have been widely used in the treatment of these patients. Unfortunately, many patients develop resistance to endocrine therapy. Tamoxifen-resistant cancer cells often exhibit higher HER2 expression and an increase of glycolysis. Our data revealed that ZBTB1 plays a critical role in tamoxifen resistance in vitro and in vivo. To see if ZBTB1 regulates HER2 expression, we tested the recruitments of ZBTB1 on HER2 regulatory sequences. We observed that over-expressed ZBTB1 occupies the estrogen receptor α (ERα)-binding site of the HER2 intron in tamoxifen-resistant cells, suppressing tamoxifen-induced transcription. In an effort to identify potential microRNAs (miRNAs) regulating ZBTB1, we found that miR-23b-3p directly targets ZBTB1. MiR-23b-3p regulates HER2 expression and tamoxifen resistance via targeting ZBTB1. Finally, we found that miR-23b-3p/ZBTB1 regulates aerobic glycolysis in tamoxifen-resistant cells. Together, our data demonstrate that ZBTB1 is a tumor suppressor in breast cancer cells and that targeting the miR-23b-3p/ZBTB1 may serve as a potential therapeutic approach for the treatment of tamoxifen resistant br...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Molecular Bases of Disease Source Type: research

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This study results in an effective target cell-specific NLS therapeutic and a general approach to guide future NLS-based development initiatives. PMID: 33024794 [PubMed]
Source: Clinical Breast Cancer - Category: Cancer & Oncology Authors: Tags: Mol Ther Methods Clin Dev Source Type: research
AbstractIntroductionPrediction models are useful to guide decision making. Our goal was to compare three published nomograms predicting axillary response to neoadjuvant chemotherapy (NAC), clinically node-positive breast cancer.MethodsPatients with cT1 –T4, cN1–N3 breast cancer treated with NAC and surgery from 2008 to 2019 were reviewed. The predicted probability of pathologic node-negative (ypN0) status was estimated for each nomogram. Area under the curve (AUC) was compared across models, overall and by biologic subtype.ResultsOf 581 patients, 253 (43.5%) were ypN0. ypN0 status varied by subtype: 23.9% for e...
Source: Annals of Surgical Oncology - Category: Cancer & Oncology Source Type: research
We reported nodal and breast downstaging rates with NET, and compared axillary response rates following NET and neoadjuvant chemotherapy (NAC).MethodsConsecutive stage I –III breast cancer patients treated with NET and surgery from January 2009 to December 2019 were identified from a prospectively maintained database. Nodal pCR rates were compared between biopsy-proven node-positive patients treated with NET, and HR+/HER2- patients treated with NAC from November 2 013 to July 2019.Results127 cancers treated with NET and 338 with NAC were included. NET recipients were older, more likely to have lobular and lower-grade...
Source: Annals of Surgical Oncology - Category: Cancer & Oncology Source Type: research
Nano LettersDOI: 10.1021/acs.nanolett.0c02644
Source: Nano Letters - Category: Nanotechnology Authors: Source Type: research
Immune response and immunotherapy play important roles in triple-negative breast cancer (TNBC). However, it is difficult to judge whether cancer is “immune-inactivated” or “immune-activated” by the carcinoma itself. The immune reaction of the microenvironment or the host to the tumor might be more informative. We assumed that clinically enlarged but pathologically negative regional lymph nodes served as an indicator for early immune response to tumors. First, we identified women with pN0 breast cancer disease from the current Surveillance, Epidemiology, and End Results database, and we compared the ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: Our findings showed how sensitivity to high NRF1 transcriptional activity coupled with its target gene signatures contribute to racial differences in luminal A and TN breast cancer subtypes. This knowledge may be useful in personalized intervention to prevent and treat this clinically challenging problem. PMID: 32705365 [PubMed - indexed for MEDLINE]
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Cancer Res Clin Oncol Source Type: research
CONCLUSIONS: IHC of single proteins or heatmap subgroups of the differentially activated PI3K/MAPK pathways was not able to discriminate patients on EVE/EXE with poor or better PFS. Upregulation of p-4EBP1 in pre-treatment biopsies as compared to levels in primary tumours pointed towards shorter PFS. PMID: 32566979 [PubMed - indexed for MEDLINE]
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Tags: J Cancer Res Clin Oncol Source Type: research
CONCLUSION: The probability of nodal positivity after neoadjuvant chemotherapy was less than 3 per cent in patients with TNBC or HER2-positive disease who achieved a breast rCR on MRI. These patients could be included in trials investigating the omission of sentinel node biopsy after neoadjuvant chemotherapy. PMID: 33031572 [PubMed - as supplied by publisher]
Source: The British Journal of Surgery - Category: Surgery Authors: Tags: Br J Surg Source Type: research
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Source: Acta Oncologica - Category: Cancer & Oncology Authors: Tags: Acta Oncol Source Type: research
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Source: Ann Oncol - Category: Cancer & Oncology Authors: Tags: Ann Surg Oncol Source Type: research
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