Mammary Cell News Volume 11.11 | Mar 28 2019

TOP STORY

Aberrant FGFR Signaling Mediates Resistance to CDK4/6 Inhibitors in ER⁺ Breast Cancer

FGFR1-amplified/ER⁺ breast cancer cells and MCF-7 cells transduced with FGFR1 were resistant to fulvestrant ± ribociclib or palbociclib. This resistance was abrogated by treatment with the FGFR tyrosine kinase inhibitor lucitanib. [Nat Commun] Full Article

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Atypical Plant Homeodomain of UBR7 Functions as an H2BK120Ub Ligase and Breast Tumor Suppressor

The authors demonstrated that the plant homeodomain (PHD) finger of ubiquitin protein ligase e3 component n-recognin7 (UBR7) harbors E3 ubiquitin ligase activity toward monoubiquitination of histone H2B at lysine120 (H2BK120Ub). Purified PHD finger or full-length UBR7 monoubiquitinated H2BK120 in vitro, and loss of UBR7 drastically reduced H2BK120Ub genome-wide binding sites in MCF10A cells. [Nat Commun] Full Article

BRCA1/BARD1-Dependent Ubiquitination of NF2 Regulates Hippo-YAP1 Signaling

Researchers showed that BRCA1 facilitated stabilization of YAP1 protein and turning “off” the Hippo pathway through ubiquitination of NF2. In BRCA1-deficient cells the Hippo pathway was “turned on.” [Proc Natl Acad Sci USA] Abstract

Acquisition of a Hybrid E/M State Is Essential for Tumorigenicity of Basal Breast Cancer Cells

Using the recently described CD104⁺/CD44^hi antigen marker combination, scientists isolated highly tumorigenic breast cancer cells residing stably—both in vitro and in vivo—in an intermediate phenotypic state and coexpressing both epithelial and mesenchymal markers. [Proc Natl Acad Sci USA] Full Article

FGFR4 Phosphorylates MST1 to Confer Breast Cancer Cells Resistance to MST1/2-Dependent Apoptosis

Using a kinase substrate screen, investigators identified mammalian sterile20-like kinase (MST)1 and MST2 among the top substrates for fibroblast growth factor receptor 4 (FGFR4). In COS-1 cells, MST1 was phosphorylated at Y433 residue in an FGFR4 kinase activity-dependent manner, as assessed by mass spectrometry. [Cell Death Differ] Full Article

Targeting AU-Rich Element-Mediated mRNA Decay with a Truncated Active Form of the Zinc-Finger Protein TIS11b/BRF1 Impairs Major Hallmarks of Mammary Tumorigenesis

Researchers showed that TIS11b was markedly underexpressed in three breast cancer cell lines, as well as in breast tumor samples. They hypothesized that restoring intracellular TIS11b levels could impair cancer cell phenotypic traits. [Oncogene] Abstract

GPNMB Augments Wnt-1 Mediated Breast Tumor Initiation and Growth by Enhancing PI3K/AKT/mTOR Pathway Signaling and β-Catenin Activity

Scientists overexpressed glycoprotein Nmb (GPNMB) in the mammary epithelium to generate MMTV/GPNMB transgenic mice and crossed these animals to the MMTV/Wnt-1 mouse model, which is known to recapitulate features of human basal breast cancers. [Oncogene] Abstract

Deciphering the Mammary Stem Cell Niche: A Role for Laminin-Binding Integrins

Investigators found that stem cell activity, as evaluated in transplantation and mammosphere assays, was reduced in mammary basal cells depleted of laminin receptors containing α3- and α6-integrin subunits. [Stem Cell Reports] Full Article

Targeting Promiscuous Heterodimerization Overcomes Innate Resistance to ERBB2 Dimerization Inhibitors in Breast Cancer

Using quantitative readouts of signaling pathway activation and cell proliferation, the authors examined their influence upon the mechanism of trastuzumab- and pertuzumab-mediated inhibition of cell growth in ERBB2-amplified breast cancer cell lines and a patient-derived xenograft model. [Breast Cancer Res] Full Article

Inhibition of USP2 Eliminates Cancer Stem Cells and Enhances TNBC Responsiveness to Chemotherapy

Investigators identified that USP2 deubiquitinating enzyme was upregulated in cancer stem cells (CSCs) and was a novel regulator of CSCs. Genetic and pharmacological targeting of USP2 substantially inhibited the self-renewal, expansion and chemoresistance of CSCs. [Cell Death Dis] Full Article

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MALAT1 Long Non-Coding RNA and Breast Cancer

The authors discuss the literature that support a pro-tumorigenic role for metastasis associated lung adenocarcinoma transcript 1 MALAT1 in order to gain potential insights into the basis of these observed differences. [RNA Biol] Abstract

Visit our reviews page to see a complete list of reviews in the mammary cell research field.

BriaCell to Announce Early Efficacy Data of Lead Candidate in Combination with KEYTRUDA^®

BriaCell Therapeutics Corp. announced it is finalizing the analysis of the initial efficacy data of the first six patients in the combination study of its lead candidate, Bria-IMT™, with pembrolizumab in advanced breast cancer. [Press release from BriaCell Therapeutics Corp. discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Odonate Therapeutics Initiates CONTESSA TRIO

Odonate Therapeutics, Inc. announced the initiation of CONTESSA TRIO, a multi-cohort, multicenter, Phase II study of tesetaxel, Odonate’s investigational, orally administered taxane. [Odonate Therapeutics, Inc.] Press Release

U.S. Food and Drug Administration Approves Puma’s NERLYNX™ (Neratinib) for Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer

Puma Biotechnology, Inc. announced that the FDA has approved NERLYNX™, formerly known as PB272, a once-daily oral tyrosine kinase inhibitor for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, following adjuvant trastuzumab-based therapy. [Puma Biotechnology, Inc.] Press Release

Atossa Genetics Announces Institutional Review Board Approval of Oral Endoxifen as Post-Mastectomy Treatment for a US Breast Cancer Patient

Atossa Genetics Inc. announced that the Institutional Review Board (IRB) has approved the use of Atossa’s oral Endoxifen as a post-mastectomy treatment in a pre-menopausal, estrogen-receptor positive breast cancer patient. This IRB approval follows the FDA’s recent “safe to proceed” letter and permits Atossa’s oral Endoxifen to be provided to the patient. [Atossa Genetics Inc.] Press Release

NIH May Bar Peer Reviewers Accused of Sexual Harassment

The National Institutes of Health (NIH) in Bethesda, Maryland, reminded the research community this week that the agency can—and sometimes does—bar scientists accused of sexual harassment from serving as peer reviewers. [ScienceInsider] Editorial

Top US Institutes Still Aren’t Reporting Clinical-Trial Results on Time

Many leading US universities are breaking the law by failing to make public the results of clinical trials. A report found that 25 of the 40 universities that sponsor the most trials in the United States did not post study results on a public, government register within 12 months of completion, as is required by US law. [Nature News] Editorial

As Elsevier Falters, Wiley Succeeds in Open-Access Deal Making

Over the last few years, Project DEAL, a consortium that represents around 700 academic institutions in Germany, has been in negotiations for nationwide licensing agreements with three of the largest scholarly publishers—Elsevier, Springer Nature, and Wiley. [The Scientist] Editorial

NEW AACR International Conference New Horizons in Cancer Research
May 3-5, 2019
Shenzhen, China

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellowship – Breast Cancer Research (Washington University School of Medicine)

Postdoctoral Position – Breast Cell Atlas (University of Cambridge)

Professor – Breast Cancer (University Hospitals Cleveland Medical Center)

Postdoctoral Researcher – BRCA1/2-Deficient Tumors (University of Oxford)

Postdoctoral Scientist – Breast Tumor Suppressor BRCA1 in DNA Repair (The George Washington University)

Postdoctoral Associate – Cancer Immunology (The Jackson Laboratory)

Scientific Review Officer – Breast Cancer (METAvivor)

Faculty Position – Breast Cancer Research (The Mayo Clinic)

Postdoctoral Fellow – Cancer Bioinformatics (BC Cancer Research Center, PHSA)

Postdoctoral Fellowship – Breast Cancer (Providence John Wayne Cancer Institute)

Postdoctoral Fellow – Breast Cancer Research (City of Hope)

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