Migration Of Triple Negative Breast Cancer Cell Line Research Articles

Repurposing mebendazole against triple-negative breast cancer CNS metastasis.

Triple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has the highest propensity among breast cancer subtypes to develop leptomeningeal disease (LMD). LMD is a spread of cancer into leptomeningeal space that speeds up the disease progression and severely aggravates the prognosis. LMD has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD. A small-molecule screen involving TNBC cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used to evaluate cell migration capacity and the effect of MBZ. For in vivo testing, CNS metastasis was introduced into BALB/c athymic nude mice through internal carotid artery injections of brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth and spread was monitored by bioluminescence imaging and immunohistochemistry. MBZ was given orally at 50 and 100mg/kg doses. MBZ bioavailability was assayed by mass spectrometry. Bioinformatic analysis and migration assays revealed higher migratory capacity of TNBC compared to other breast cancer subtypes. MBZ effectively slowed down migration of TNBC cell line MDA-MB-231 and its brain tropic derivative MDA-MB-231-BR. In animal studies, MBZ reduced leptomeningeal spread, and extended survival in brain metastasis model produced by MDA-MB-231-BR cells. MBZ did not have an effect in the non-migratory MCF7-BR model. We demonstrated that MBZ is a safe and effective oral agent in an animal model of TNBC CNS metastasis. Our findings are concordant with previous efforts involving MBZ and CNS pathology and support the drug's potential utility to slow down leptomeningeal spread.

MiR-4646-5p Acts as a Tumor-Suppressive Factor in Triple Negative Breast Cancer and Targets the Cholesterol Transport Protein GRAMD1B.

MicroRNAs (miRNAs) are crucial post-transcriptional regulators of gene expression, and their deregulation contributes to many aspects of cancer development and progression. Thus, miRNAs provide insight into oncogenic mechanisms and represent promising targets for new therapeutic approaches. A type of cancer that is still in urgent need of improved treatment options is triple negative breast cancer (TNBC). Therefore, we aimed to characterize a novel miRNA with a potential role in TNBC. Based on a previous study, we selected miR-4646-5p, a miRNA with a still unknown function in breast cancer. We discovered that higher expression of miR-4646-5p in TNBC patients is associated with better survival. In vitro assays showed that miR-4646-5p overexpression reduces growth, proliferation, and migration of TNBC cell lines, whereas inhibition had the opposite effect. Furthermore, we found that miR-4646-5p inhibits the tube formation ability of endothelial cells, which may indicate anti-angiogenic properties. By whole transcriptome analysis, we not only observed that miR-4646-5p downregulates many oncogenic factors, like tumor-promoting cytokines and migration- and invasion-related genes, but were also able to identify a direct target, the GRAM domain-containing protein 1B (GRAMD1B). GRAMD1B is involved in cellular cholesterol transport and its knockdown phenocopied the growth-reducing effects of miR-4646-5p. We thus conclude that GRAMD1B may partly contribute to the diverse tumor-suppressive effects of miR-4646-5p in TNBC.

Hydroxypropyl-β-cyclodextrin inhibits the development of triple negative breast cancer by enhancing antitumor immunity

Triple negative breast cancer (TNBC) is regarded as one of the most aggressive forms of breast cancer. Hydroxypropyl-β-cyclodextrin (HP-β-CD) has been used as a therapeutic agent for Niemann-Pick disease Type C (NPC). However, the exact actions and mechanisms of HP-β-CD on TNBC are not fully understood. To examine the influence of HP-β-CD on the proliferation and migration of TNBC cell lines, particularly 4T1 and MDA-MB-231 cells, a range of assays, including MTT, scratch, cell cycle, and clonal formation assays, were performed. Furthermore, the effectiveness of HP-β-CD in the treatment of TNBC was assessed in vivo using a 4T1 tumor-bearing BALB/c mouse model. We demonstrated the anti-proliferation and anti-migration effect of HP-β-CD on TNBC both in vitro and in vivo. High cholesterol diet can attenuate HP-β-CD-inhibited TNBC growth. Mechanistically, HP-β-CD reduced tumor cholesterol levels by increasing ABCA1 and ABCG1-mediated cholesterol reverse transport. HP-β-CD promoted the infiltration of T cells into the tumor microenvironment (TME) and improved exhaustion of CD8+ T cells via reducing immunological checkpoint molecules expression. Additionally, HP-β-CD inhibited the recruitment of tumor associated macrophages to the TME via reducing CCL2-p38MAPK-NF-κB axis. HP-β-CD also inhibited the epithelial mesenchymal transition (EMT) of TNBC cells mediated by the TGF-β signaling pathway. In summary, our study suggests that HP-β-CD effectively inhibited the proliferation and metastasis of TNBC, highlighting HP-β-CD may hold promise as a potential antitumor drug.

Network Pharmacology and Experimental Validation to Explore the Effect and Mechanism of Kanglaite Injection Against Triple-Negative Breast Cancer.

Kanglaite injection (KLTi), made of Coix seed oil, has been shown to be effective in the treatment of numerous cancers. However, the anticancer mechanism requires further exploration. This study aimed to investigate the underlying anticancer mechanisms of KLTi in triple-negative breast cancer (TNBC) cells. Public databases were searched for active compounds in KLTi, their potential targets and TNBC-related targets. KLTi's core targets and signaling pathways were determined through compound-target network, protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecular docking was carried out to predict the binding activity between active ingredients and key targets. In vitro experiments were conducted to further validate the predictions of network pharmacology. Fourteen active components of KLTi were screened from the database. Fifty-three candidate therapeutic targets were selected, and bioinformatics analysis was performed to identify the top two active compounds and three core targets. GO and KEGG enrichment analyses indicated that KLTi exerts therapeutic effects on TNBC through the cell cycle pathway. Molecular docking results showed that the main compounds of KLTi exhibited good binding activity to key target proteins. Results from in vitro experiments showed that KLTi inhibited proliferation and migration of TNBC cell lines 231 and 468, induced apoptosis, blocked cells in the G2/M phase, downregulated the mRNA expression of seven G2/M phase-related genes cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 2 (CDK2), and checkpoint kinase 1 (CHEK1), cell division cycle 25A (CDC25A), cell division cycle 25B (CDC25B), maternal embryonic leucine zipper kinase (MELK), and aurora kinase A (AURKA), as well as downregulated CDK1 protein expression and up-regulated protein expression of Phospho-CDK1. By utilizing network pharmacology, molecular docking, and in vitro experiments, KLTi was confirmed to have anti-TNBC effects by arresting cell cycle and inhibiting CDK1 dephosphorylation.

Cytokines secreted from adipose tissues mediate tumor proliferation and metastasis in triple negative breast cancer

BackgroundObesity is a high-risk factor for development and poor prognosis of triple-negative breast cancer (TNBC), which was considered as a high malignant and poor clinical outcome breast cancer subtype. TNBC proliferation and migration regulated by obesity is complex. Here, we studied effects of cytokines secreted from adipose tissue on development of TNBC.MethodsForty postmenopausal cases by Yuebei People’s Hospital of Shaoguan with stage I/IIA TNBC were enrolled. Cytokine concentrations were examined using ELISA analysis. Proliferation and migration of TNBC cell lines were performed using CCK8 assays and Transwell tests. The Log-rank (Mantel-Cox) test, two-tailed Mann-Whitney U test and two-tailed unpaired t test were performed using GraphPad Prism 8.4.2.ResultsSurvival analysis indicated that obese patients with TNBC had worse disease free survival (DFS) as compared with normal weight group (Hazard Ratio 4.393, 95% confidence interval (CI) of ratio 1.071–18.02, p < 0.05). Obese patients with TNBC had severe insulin resistance and high plasma triglycerides. However, plasma adiponectin concentration was decreased and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration was increased in obese TNBC patients as compared with the nonobese group. The similar results were found in the cytokine secretion from adipose tissues and insulin-resistant adipocytes. The secretion of adipose tissue from obese TNBC patients could promote proliferation and migration of TNBC cell lines, including MDA-MB-157, MDA-MB-231, MDA-MB-453 and HCC38 cells. These TNBC cell lines co-incubated with insulin-resistant 3T3-L1 adipocytes or supplementing these cytokines medium also exhibited increase of proliferative and migratory capacity.ConclusionTNBC patients with obesity had worse prognosis compared with the normal weight groups. Alteration of cytokines secreted from adipose tissues mediated proliferation and migration of TNBC, leading to tumor progression in TNBC patients with obesity.

MicroRNA-192-5p inhibits migration of triple negative breast cancer cells and directly regulates Rho GTPase activating protein 19.

Among the different breast cancer subtypes, triple-negative breast cancer (TNBC) is associated with a poor prognosis, low survival rates, and high expression of histone deacetylases. Treatment with histone deacetylase inhibitor trichostatin A (TSA) leads to an increased expression of potential tumor-suppressive miRNAs. Characterization of these miRNAs can help to find new molecular targets for treatment of TNBC. We identified differentially expressed miRNAs by microarray analyses after treatment with TSA in the TNBC cell lines HCC38, HCC1395, and HCC1935. The gene locus of hsa-miRNA-192-5p (miR-192) and hsa-miR-194-2 (miR-194-2) with its host gene, long noncoding RNA miR-194-2HG, has been linked to inhibition of migration in different tumor types. Therefore, we examined tumor-relevant functional effects using WST-1-based proliferation, capsase-3/7-based apoptosis, and trans-well migration assays after transfection with miRNA mimics or specific siRNAs. We demonstrated the tumor-suppressive capacity of miR-192 in TNBC cells, which was exerted through inhibition of proliferation, induction of apoptosis, and reduction of migration. Gene expression and bioinformatics analyses of TNBC cell lines transfected with miR-192 mimics, identified a number of genes involved in migration including the Rho GTPase Activating Protein ARHGAP19. Through RNA immunoprecipitation we demonstrated the direct binding of miR-192 and ARHGAP19. Downregulation of ARHGAP19 expression by either miR-192 or siRNA inhibited migration of TNBC cells significantly. Our findings demonstrate that overexpression of epigenetically deregulated miR-192 decreases proliferation, promotes apoptosis, and inhibits migration of TNBC cell lines.

Abstract 2322: Targeting glutamine transporter (ASCT2) inhibits metabolic stress-induced GD2+ cancer stem cell-like phenotype in triple-negative breast cancer

Abstract Nutrient deprivation is one of the hallmark conditions of a rapidly growing tumor. Rapid proliferation of tumor cells leads to increased consumption of metabolites such as glucose and glutamine resulting in metabolic stress. However, phenotypic and functional status of tumor cells under these conditions is not clear. We hypothesize that nutrient deprivation-induced metabolic stress results in a breast cancer stem cell-like (BCSC) phenotype in triple negative breast cancer (TNBC). We found that serum-deprived conditions result in significant upregulation of GD2+ cells compared to serum rich conditions: from 9%±2% to 26%±5% in MDA-MB-231 and 7%±2% to 29%±5% in SUM159 cells. Interestingly, this affect was compensated when the cells were supplemented with serum-rich medium. In addition, a positive correlation was observed between GD2+ cell number and tumor volume in vivo, suggesting metabolic stress in the growing tumors results in GD2+ phenotype in TNBC cells. Next, TNBC cells cultured under glucose deprivation or in the presence of glycolysis inhibitor, 2-deoxy glucose (2DG) showed a 2-fold increase in GD2+ cells compared to cells cultured with glucose (6g/L) or without 2DG, suggesting that glucose deprivation enhances GD2 expression. Nutrient deprived conditions also showed a significant increase in the expression of stress markers ATF4 and SESN2 demonstrating TNBC cells under metabolic stress. In addition, the above conditions also showed a 2.5-fold upregulation of the mammosphere formation in TNBC cells compared to nutrient rich conditions. Global metabolomics profiling identified glutathione biosynthesis to be most highly upregulated in GD2+ cells. Furthermore, we found that supplementation of glutamine (precursor for glutathione biosynthesis) increases the percentage of GD2+ cells. Carbon and nitrogen tracing using 13C- and 15N-labeled glutamine by mass spectrometry showed its direct contribution to GD2 biosynthesis. Treatment with glutamine transporter (ASCT2) inhibitor V9302 reduced GD2+ cell number by 70%-80% in TNBC cell lines and dramatically inhibited mammosphere and soft agar colony formation, and migration of TNBC cell lines. Mechanistic studies revealed that V9302 inhibits glutathione pathway and induces ROS levels in TNBC cells. Additionally, V9302 treatment inhibited AKT-ERK-mTOR-4E-BP1 pathway and combination of V9302 with paclitaxel synergizes TNBC cell killing. We also identified that, V9302 treatment induced ferroptosis (iron-dependent cell death) in TNBC cells. Finally, V9302 treatment significantly inhibited tumor growth (p&amp;lt;0.0001) in TNBC-PDX model. In conclusion, metabolic stress results in GD2+ BCSC phenotype in TNBC cells and glutamine directly contributes to GD2 biosynthesis. Targeting ASCT2 could complement conventional chemotherapy in TNBC. Citation Format: Appalaraju Jaggupilli, Stanley Ly, Khoa Nguyen, Roshan Borkar, Bin Yuan, Danthasinghe Waduge Piyarathna, Yuanqing Yan, Helen Piwnica-Worms, Henry Charles Manning, Michael Andreeff, Nagireddy Putluri, Lokesh Battula. Targeting glutamine transporter (ASCT2) inhibits metabolic stress-induced GD2+ cancer stem cell-like phenotype in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2322.

Anti-Cancer Effects of an Optimised Combination of Ginsenoside Rg3 Epimers on Triple Negative Breast Cancer Models.

Key problems of chemotherapies, as the mainstay of treatment for triple-negative breast cancer (TNBC), are toxicity and development of tumour resistance. Using response surface methodology, we previously optimised the combination of epimers of ginsenoside Rg3 (Rg3) for anti-angiogenic action. Here, we show that the optimised combination of 50 µM SRg3 and 25 µM RRg3 (C3), derived from an RSM model of migration of TNBC cell line MDA-MB-231, inhibited migration of MDA-MB-231 and HCC1143, in 2D and 3D migration assays (p < 0.0001). C3 inhibited mammosphere formation efficiency in both cell lines and decreased the CD44+ stem cell marker in the mammospheres. Molecular docking predicted that Rg3 epimers had a better binding score with IGF-1R than with EGFR, HER-2 or PDGFR, and predicted an mTOR inhibitory function of Rg3. C3 affected the signalling of AKT in MDA-MB-231 and HCC1143 mammospheres. In a mouse model of metastatic TNBC, an equivalent dose of C3 (23 mg/kg SRg3 + 11 mg/kg RRg3) or an escalated dose of 46 mg/kg SRg3 + 23 mg/kg RRg3 was administered to NSG mice bearing MDA-MB-231-Luc cells. Calliper and IVIS spectrum measurement of the primary and secondary tumour showed that the treatment shrunk the primary tumour and decreased the load of metastasis in mice. In conclusion, this combination of Rg3 epimers showed promising results as a potential treatment option for TNBC patients.

Biological and clinical significance of flap endonuclease‑1 in triple‑negative breast cancer: Support of metastasis and a poor prognosis.

Flap endonuclease-1 (FEN1), a structure-specific nuclease participating in DNA replication and repair processes, has been confirmed to promote the proliferation and drug resistance of tumor cells. However, the biological functions of FEN1 in cancer cell migration and invasion have not been defined. In the present study, using online database analysis and immunohistochemistry of the specimens, it was found that FEN1 expression was associated with a highly invasive triple-negative breast cancer (TNBC) subtype in both breast cancer samples from the Oncomine database and from patients recruited into the study. Furthermore, FEN1 was an important biomarker of lymph node metastasis and poor prognosis in patients with TNBC. FEN1 promoted migration of TNBC cell lines and FEN1 knockdown reduced the number of spontaneous lung metastasis in vivo. Ingenuity Pathway Analysis of FEN1-related transcripts in 198 patients with TNBC demonstrated that the polo-like kinase family may be the downstream target of FEN1. PLK4 was further identified as a critical target of FEN1 mediating TNBC cell migration, by regulating actin cytoskeleton rearrangement. The results of the present study validate FEN1 as a therapeutic target in patients with TNBC and revealed a new role for FEN1 in regulating TNBC invasion and metastasis.

PIBF1 suppresses the ATR/CHK1 signaling pathway and promotes proliferation and motility of triple-negative breast cancer cells

This study evaluates the oncogenic role of PIBF1 in triple-negative breast cancer (TNBC). TNBC is considered to have a poorer prognosis than other types of breast cancer and is associated with high risk of recurrence and distant metastasis. Currently, there are no effective therapies for the TNBC patients with distant metastasis due to the lack of targeted therapeutic options. The effects of PIBF1 knockdown on the cell viability and motility of TNBC cell lines were investigated. Effects of PIBF1 overexpression on tumorigenicity and cell motility were confirmed using Ba/F3 cell line and xenograft study on BALB/c nude mice. In TNBC cell lines that highly express PIBF1, knockdown of PIBF1 induces apoptosis and suppresses cell viability and motility with activation of the ATR/CHK1 signaling pathway. Moreover, the oncogenic function of PIBF1 was confirmed using the Ba/F3 cell line. For the first time, these findings clarify the role of PIBF1 in regulating ATR/CHK1 signaling pathway and inhibiting the proliferation and migration of TNBC cell lines. These results demonstrate the oncogenic roles of PIBF1 and provide new insights into the function and the molecular mechanism of PIBF1 in malignant TNBC.

Synergistic anticancer action of quercetin and curcumin against triple-negative breast cancer cell lines.

Women with the breast cancer type 1 susceptibility protein (BRCA1) mutation and loss of BRCA1 expression are reported to have an increased risk of triple-negative breast cancer (TNBC). Targeting BRCA1 modulation might offer a therapeutic option to treat TNBC patients. Our studies detected that BRCA1 is poorly expressed in TNBC cell lines and highly expressed in ER+ breast cancer cell lines. To modulate BRCA1 expression, we tested two different dietary components to find out if any would induce tumor suppressor genes. We detected that quercetin and curcumin dose-dependently enhanced the BRCA1 expression. Further, a synergistic action of quercetin and curcumin was observed in modulating the BRCA1 level and in inhibiting the cell survival and migration of TNBC cell lines. Quercetin and curcumin appeared to induce BRCA1 promoter histone acetylation. Furthermore, BRCA1 knockdown induced cell survival and cell migration in ER + cells were significantly decreased by the combined treatment of quercetin and curcumin. Our present study concluded that the combination treatment of quercetin and curcumin acts synergistically to induce anticancer activity against TNBC cells by modulating tumor suppressor genes.

Folic-Acid-Adorned PEGylated Graphene Oxide Interferes with the Cell Migration of Triple Negative Breast Cancer Cell Line, MDAMB-231 by Targeting miR-21/PTEN Axis through NFκB.

Triple negative breast cancer (TNBC), characterized by its aggressive and highly metastatic nature, is difficult to cure by the currently available therapies. In our investigation, folic-acid-adorned PEGylated graphene oxide (FA-PEG-GO) was synthesized by modifying graphene oxide (GO) with folic acid-PEG conjugate (FA-PEG-NH2) by EDC/NHS coupling reaction. FA-PEG-GO exhibited an exceptional potential to attenuate cell migration of TNBC cell line ,MDAMB-231 as compared to GO because of the adorned folic acid moiety, which rendered better targeting. FA-PEG-GO inhibited cell migration by actin depolymerization and perturbing lamellipodia formation. The immunocytochemistry and western blot data unraveled the fact that FA-PEG-GO inhibited cell migration by targeting miR-21 by restricting the nuclear translocation of NFκB. The downregulation of miR-21 resulted in the elevation of PTEN expression which sequentially downregulated pFAK resulting in inhibition of cell migration. Moreover, upregulation of PTEN in FA-PEG-GO treated cells led to the decrease in expression of the downstream regulators including pAkt(Ser473) and pERK1/2, which contributed to the retardation of cell migration. Interestingly, the overexpression of NFκB-p65 by the transfection of NFκB-p65 expression plasmid in TNBC cells reversed the inhibitory effect of FA-PEG-GO on the nuclear translocation of NFκB-p65 which stabilized miR-21 expression and successively downregulated PTEN expression in FA-PEG-GO treated cells. Furthermore, miR-21 overexpression by transfection of miR-21 mimic in turn downregulated PTEN expression and sequentially restored the expression of pFAK even upon FA-PEG-GO treatment. miR-21 overexpression also compensated the inhibitory effect of FA-PEG-GO on pAkt(Ser473) and pERK1/2 which was evident from their significant expression in FA-PEG-GO-treated cells. The studies on chick embryo model ratified the ex ovo antimigratory efficacy of FA-PEG-GO. Altogether, our study unveiled the enormous potential of FA-PEG-GO to attenuate migration of TNBC cell line, MDAMB-231 by targeting the miR-21/PTEN axis through NFκB and thereby providing insights on cancer treatment.

Abstract P6-03-11: Erk5 as a therapeutic target in triple negative breast cancer (TNBC)

Abstract TNBC is a subtype of breast cancer known for its aggressive behavior and poor prognosis. TNBC accounts for 17-24% of all invasive breast cancers and is a subtype that lacks the expression of hormone receptors; oestrogen [ER], progesterone [PR]) and epidermal growth factor receptor 2 (HER2) receptors. Currently there has been a shift from using empirically derived agents that inhibit tumor cell growth and/or survival, to molecular therapies that target specific molecules that regulate these and other important biological processes. Despite the success of some new-targeted therapies to treat breast cancer, the outlook for the majority of patients with TNBC remains poor. Therefore we have utilized the KinexTM antibody array to resolve potential new targetable "nodes". We have screened 43 primary breast cancer biopsies (16 TNBC, 16 ER/PR positive and 11 HER2-positive) and 16 breast cancer cell lines for protein/phosphoprotein levels. Extracellular-signal-regulated kinase 5 (Erk5) is a member of the MAPK family. Erk5 has a large, unique C-terminal-half not found in other MAPK family members and because of this unique 400-amino acid extension, ERK5 is also called big MAP kinase 1 (BMK1). By extensive in silico analyses, we identified that the Erk5 metagene is prognostic and identifies TNBC/BLBC with poor prognosis. Our kinome study of primary breast cancer has further confirmed that the MEK5-Erk5 pathway is upregulated in the TNBC subgroup compared to the other TNBC subgroups and that pharmacological inhibition of Erk5 is therapeutic against primary MDA-MB-231 TNBC xenografts (1). Our preliminary data has shown that Erk5 is overexpressed in the TNBC subtype at the protein level. We have also shown that silencing Erk5 by siRNA or shRNA inhibits migration of TNBC cell lines in vitro. Expression of Erk5 (total and phosphoproteins) will be investigated in primary breast tumours and metastases samples from patient by immunohistochemistry. We will also overexpress Erk5 in non-metastatic breast cancer cell lines to study the effect of Erk5 overexpression on metastases. In an elegant study, site directed mutagenesis was used to modify Erk5 and show that phosphorylations of the C-terminal domain of kinase activated Erk5 is required for the transcriptional activity of Erk5. Using in vitro and in vivo models we will determine if the transcriptional activity of activated Erk5 is a major player to drive metastatic phenotype. Moreover, whether kinase-dependent or transcription-dependent activity of Erk5 on several pathways is sufficient to drive metastasis will also be determined. Our results strongly suggest the MEK5-Erk5 pathway as a prognostic and therapeutic pathway in a poor-prognosis subset of TNBC/BCLC. Characterization of this pathway in clinical cohorts particularly in TNBC tumors, mechanistic understanding of its contribution to metastasis and therapeutic targeting in vivo would help develop a personalised approach to identify and treat TNBC tumors and metastases with activated Erk5 pathway. 1. Al-Ejeh F, Miranda M et al. Kinome profiling reveals breast cancer heterogeneity and identifies targeted therapeutic opportunities for triple negative breast cancer. Oncotarget. March 19, 2014. Citation Format: Mariska Sauzine Miranda, Fares Al Ejeh, Wei Shi, Peter Simpson, Sunil Lakhani, Kum Kum Khanna. Erk5 as a therapeutic target in triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-03-11.