YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer

Rana, Priyanka S.; Alkrekshi, Akram; Markovic, Vesna; Khiyami, Amer; Chan, RV Paul; Perzynski, Adam T.; Joseph, Natalie E.; Sossey‐Alaoui, Khalid

doi:10.3390/cancers13246262

Cited by 7 publications

(6 citation statements)

References 66 publications

(83 reference statements)

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“…By including measures of neighborhood characteristics in combination with clinical variables from a tumor registry and EHR, our ndings extend insights provided by prior studies [7,19,50,51], which have been constrained by the lack of availability of geocoded addresses, comorbidities, and other indicators in tumor registries. Incorporating the ADI to measure neighborhood socioeconomic position alongside patient-reported racial background enabled our study to evaluate the overlapping contributions of socioeconomic position and race more comprehensively.…”

Section: Discussionsupporting

confidence: 70%

Neighborhood and racial influences on triple negative breast cancer: evidence from Northeast Ohio

Eom

Berg²,

Joseph³

et al. 2023

Breast Cancer Res Treat

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Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher recurrence rates and poorer prognoses and most prevalent among non-Hispanic Black women. Studies of multiple health conditions and care processes suggest that neighborhood socioeconomic position is a key driver of health disparities. We examined roles of patients' neighborhood-level characteristics and race on prevalence, stage at diagnosis, and mortality among patients diagnosed with BC at a large safety-net healthcare system in Northeast Ohio. MethodsWe used tumor registry to identify BC cases from 2007-2020 and electronic health records and American Community Survey for individual-and area-level factors. We performed multivariable regression analyses to estimate associations between neighborhood-level characteristics, measured by the Area Deprivation Index (ADI), race and comparative TNBC prevalence, stage at diagnosis, and total mortality. ResultsTNBC was more common among non-Hispanic Black (53.7%) vs. non-Hispanic white patients (46.4%). Race and ADI were individually signi cant predictors of TNBC prevalence, stage at diagnosis, and total mortality. Race remained signi cantly associated with TNBC subtype, adjusting for covariates. Accounting for TNBC status, a more disadvantaged neighborhood was signi cantly associated with a worse stage at diagnosis and higher death rates. ConclusionOur ndings suggest that both neighborhood socioeconomic position and race are strongly associated with TNBC vs. other BC subtypes. The burden of TNBC appears to be highest among Black women in the most socioeconomically disadvantaged neighborhoods. Our study suggests a complex interplay of social conditions and biological disease characteristics contributing to racial disparities in BC outcomes.

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Section: Discussionsupporting

confidence: 70%

Neighborhood and racial influences on triple negative breast cancer: evidence from Northeast Ohio

Eom

Berg²,

Joseph³

et al. 2023

Breast Cancer Res Treat

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“…ChemiDoc MP Imaging system (Bio-Rad) was used for image acquisition of developed gels. Signal intensity of WB bands was quantitatively analyzed by ImageJ software, as described previously [ 19 ] and according to the parameters described in ImageJ user guide ( http://rsbweb.nih.gov/ij/docs/guige/146.html ).…”

Section: Methodsmentioning

confidence: 99%

The WAVE3/β-catenin oncogenic signaling regulates chemoresistance in triple negative breast cancer

et al. 2023

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Background Metastatic breast cancer is responsible for the death of the majority of breast cancer patients. In fact, metastatic BC is the 2nd leading cause of cancer-related deaths in women in the USA and worldwide. Triple negative breast cancer (TNBC), which lacks expression of hormone receptors (ER-α and PR) and ErbB2/HER2, is especially lethal due to its highly metastatic behavior, propensity to recur rapidly, and for its resistance to standard of care therapies, through mechanisms that remain incompletely understood. WAVE3 has been established as a promoter of TNBC development and metastatic progression. In this study, we investigated the molecular mechanisms whereby WAVE3 promotes therapy-resistance and cancer stemness in TNBC, through the regulation of β-catenin stabilization. Methods The Cancer Genome Atlas dataset was used to assess the expression of WAVE3 and β-catenin in breast cancer tumors. Kaplan–Meier Plotter analysis was used to correlate expression of WAVE3 and β-catenin with breast cancer patients’ survival probability. MTT assay was used to quantify cell survival. CRISPR/Cas9-mediated gene editing, 2D and 3D tumorsphere growth and invasion assays, Immunofluorescence, Western blotting, Semi-quantitative and real-time quantitative PCR analyses were applied to study the WAVE3/β-catenin oncogenic signaling in TNBC. Tumor xenograft assays were used to study the role of WAVE3 in mediating chemotherapy resistance of TNBC tumors. Results Genetic inactivation of WAVE3 in combination of chemotherapy resulted in inhibition of 2D growth and 3D tumorsphere formation and invasion of TNBC cells in vitro, as well as tumor growth and metastasis in vivo. In addition, while re-expression of phospho-active WAVE3 in the WAVE3-deficient TNBC cells restored the oncogenic activity of WAVE3, re-expression of phospho-mutant WAVE3 did not. Further studies revealed that dual blocking of WAVE3 expression or phosphorylation in combination with chemotherapy treatment inhibited the activity and expression and stabilization of β-catenin. Most importantly, the combination of WAVE3-deficiency or WAVE3-phospho-deficiency and chemotherapy suppressed the oncogenic behavior of chemoresistant TNBC cells, both in vitro and in vivo. Conclusion We identified a novel WAVE3/β-catenin oncogenic signaling axis that modulates chemoresistance of TNBC. This study suggests that a targeted therapeutic strategy against WAVE3 could be effective for the treatment of chemoresistant TNBC tumors.

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“…Immunoblotting analyses were conducted as previously described with some modification ( Ou et al, 2014 ; Shebaby et al, 2014 ; Rana et al, 2021 ). MDA-MB-231 cells were seeded at a density of 4 × 10 6 /mL per 10-cm Petri dish, and incubated at 37°C with 5% CO 2 until 90% confluence was achieved.…”

Section: Methodsmentioning

confidence: 99%

Alginate-based hydrogel platform embedding silver nanoparticles and cisplatin: characterization of the synergistic effect on a breast cancer cell line

Maher,

Kalil,

Liu

et al. 2023

Front. Mol. Biosci.

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Introduction: Breast cancer is a significant cause of mortality in women globally, and current treatment approaches face challenges due to side effects and drug resistance. Nanotechnology offers promising solutions by enabling targeted drug delivery and minimizing toxicity to normal tissues.Methods: In this study, we developed a composite platform called (Alg-AgNPs-CisPt), consisting of silver nanoparticles coated with an alginate hydrogel embedding cisplatin. We examined the effectiveness of this nanocomplex in induce synergistic cytotoxic effects on breast cancer cells.Results and Discussion: Characterization using various analytical techniques confirmed the composition of the nanocomplex and the distribution of its components. Cytotoxicity assays and apoptosis analysis demonstrated that the nanocomplex exhibited greater efficacy against breast cancer cells compared to AgNPs or cisplatin as standalone treatments. Moreover, the nanocomplex was found to enhance intracellular reactive oxygen species levels, further validating its efficacy. The synergistic action of the nanocomplex constituents offers potential advantages in reducing side effects associated with higher doses of cisplatin as a standalone treatment. Overall, this study highlights the potential of the (Alg-AgNPs-CisPt) nanocomplex as a promising platform embedding components with synergistic action against breast cancer cells.

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YB1 Is a Major Contributor to Health Disparities in Triple Negative Breast Cancer

Cited by 7 publications

References 66 publications

Neighborhood and racial influences on triple negative breast cancer: evidence from Northeast Ohio

Neighborhood and racial influences on triple negative breast cancer: evidence from Northeast Ohio

The WAVE3/β-catenin oncogenic signaling regulates chemoresistance in triple negative breast cancer

Alginate-based hydrogel platform embedding silver nanoparticles and cisplatin: characterization of the synergistic effect on a breast cancer cell line

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