Mammary Cell News Volume 11.42 | Oct 31 2019

TOP STORY

Therapeutic Targeting of CDK12/CDK13 in Triple-Negative Breast Cancer

Researchers report the development of SR-4835, a highly selective dual inhibitor of cyclin-dependent kinases (CDK)12 and CDK13, which disabled triple-negative breast cancer cells. Mechanistically, inhibition or loss of CDK12/CDK13 triggered intronic polyadenylation site cleavage that suppressed the expression of core DNA damage response proteins. [Cancer Cell] Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Methylation-Mediated Silencing of miR-133a-3p Promotes Breast Cancer Cell Migration and Stemness via miR-133a-3p/MAML1/DNMT3A Positive Feedback Loop

qRT-PCR was applied to detect the expression of miR-133a-3p in breast cancer tissues and cell lines. Bisulfite sequencing was used to detect the degree of methylation of the miR-133a-3p promoter. [J Exp Clin Cancer Res] Full Article

Targeting of Prostate-Specific Membrane Antigen for Radio-Ligand Therapy of Triple-Negative Breast Cancer

Triple-negative breast cancer cells MDA-MB231 showed a high pro-angiogenetic potential on tube formation of endothelial HUVEC cells. The induced endothelial expression of prostate-specific membrane antigen (PSMA) was efficiently addressed by radiolabeled PSMA-specific ligands. ¹⁷⁷Lu-labeled PSMA-617 strongly impaired the vitality and angiogenic potential of HUVEC cells. [Breast Cancer Res] Full Article

Acetylation of Ezrin Regulates Membrane-Cytoskeletal Interaction Underlying CCL18-Elicited Cell Migration

Researchers showed that ezrin is acetylated by PCAF in breast cancer cells in response to CCL18 stimulation. Ezrin physically interacted with PCAF and was a cognate substrate of PCAF. The acetylation site of ezrin was mapped by mass spectrometric analyses and dynamic acetylation of ezrin was essential for CCL18-induced breast cancer cell migration and invasion. [J Mol Cell Biol] Abstract

Downregulation of GRK5 Hampers the Migration of Breast Cancer Cells

Investigators demonstrated that decreased GRK5 expression induced by knock-down experiments or sunitinib treatment hampered the migration of cancer cell lines. A proteomic analysis revealed many pathways related to cell migration which were down regulated upon the GRK5 knock-down. [Sci Rep] Full Article

Tumor-Secreted Hsp90α on External Surface of Exosomes Mediates Tumor – Stromal Cell Communication via Autocrine and Paracrine Mechanisms

The authors showed that extracellular heat shock protein-90alpha (eHsp90α) accounted for approximately 1% of total cellular Hsp90α and was associated with tumor-secreted exosomes. CRISPR-cas9 knockout of Hsp90α did not affect the overall distribution and quantity of secreted exosomes, but it caused increased exosome-associated CD9 and decreased exosome-associated TSG101, Alix, and CD63. [Sci Rep] Full Article

Screening Antiproliferative Drug for Breast Cancer From Bisbenzylisoquinoline Alkaloid Tetrandrine and Fangchinoline Derivatives by Targeting BLM Helicase

Fluorescence polarization technique was used to screen small molecules which inhibited the DNA binding and unwinding of bloom syndrome (BLM)^642-1290 helicase. The effects of positive small molecules on the ATPase and conformation of BLM^642-1290 helicase were studied by the malachite green-phosphate ammonium molybdate colorimetry and ultraviolet spectral scanning, respectively. [BMC Cancer] Full Article

Novel lncRNA PSMG3-AS1 Functions as a miR-143-3p Sponge to Increase the Proliferation and Migration of Breast Cancer Cells

The relative expression levels of long non-coding (lnc)RNA PSMG3-antisense (AS)1 and microRNA (miR)-143-3p were determined using reverse-transcription quantitative PCR. The protein expression levels of collagen type 1 alpha 1 and proliferating cell nuclear antigen were obtained using western blot analysis. [Oncol Rep] Abstract

Comprehensive Bioinformatics Study Reveals Targets and Molecular Mechanism of Hesperetin in Overcoming Breast Cancer Chemoresistance

Microarray data obtained after hesperetin treatment in the NCI-60 cell line panel collection were retrieved from the COMPARE public library. These data were then compared with the list of the regulatory genes of breast cancer resistance obtained from PubMed and further analyzed for gene ontology and KEGG pathway enrichment, as well as protein–protein interaction network. [Mol Divers] Abstract | Graphical Abstract

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Recent Advances in Nanotheranostics for Triple Negative Breast Cancer Treatment

The authors provide basic insight and understanding of the novel nano-therapeutic modalities in triple-negative breast cancer diagnosis and treatment and to sensitize the readers for continue designing the novel nanomedicine. This is the first time that designing nano-particles with stoichiometric definable number of antibodies per nanoparticle now represents the next level of precision by design in nanomedicine. [J Exp Clin Cancer Res] Full Article

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Seattle Genetics Announces Positive Topline Results from Pivotal Trial of Tucatinib in Locally Advanced or Metastatic HER2-Positive Breast Cancer

Seattle Genetics, Inc. announced positive topline results from the HER2CLIMB trial, a randomized, double-blind, placebo-controlled, active comparator pivotal trial evaluating tucatinib. The trial compared tucatinib in combination with trastuzumab and capecitabine to trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer. [Seattle Genetics, Inc.] Press Release

The Mary Kay Foundation Awards $3.1 Million in Cancer Research and Domestic Violence Shelter Grants

After reviewing more than 70 applications, The Mary Kay Foundation Research Review Committee awarded $100,000 grants to 11 cancer research institutions across the country, totaling $1.1 million. [The Mary Kay Foundation (The Financial Post)] Press Release

Swiss Authorities Probe Boehringer Ingelheim and Other Companies for Antitrust Practices

A Swiss government agency that last month opened an antitrust investigation into several drug makers and distributors has now disclosed the names of nearly a dozen companies that may have fixed the market for an ingredient used to make a treatment for stomach pain. [STAT News] Editorial

Increase in Academics Leaving the UK Since Brexit Vote

After the 2016 Brexit referendum, in which voters decided to have the UK leave the European Union (EU), the number of academics from EU countries leaving the United Kingdom for other university jobs increased by almost half, according to Times Higher Education. [The Scientist] Editorial

PhD-Turned-Policy Insider Takes Over World’s Largest Science Society

In January 2020, the 46-year-old structural biologist Sudip Parikh will become the new CEO of AAAS (which publishes Science) as the 171-year-old association pursues its mission to advance science and serve society. [ScienceInsider] Editorial

NEW Translational Cancer Research for Basic Scientists Workshop
November 17-22, 2019
Boston, Massachusetts, United States

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

NEW Postdoctoral Fellow – Breast Cancer Stem Cells (Dalhousie University)

NEW Research Scholar – Breast Cancer (Eastern Virginia Medical School)

Research Associate – Breast Cancer In Vivo Modeling (King’s College London)

Postdoctoral Scholar – Breast Cancer (The University of Kentucky)

Postdoctoral Researcher – Breast and Ovarian Cancer (Curtin University)

Postdoctoral Position – Cancer Biology (Memorial Sloan Kettering Cancer Center)

Research Scientist – Breast Cancer (The University of Pittsburgh)

Postdoctoral Researcher – Nanomedicine and Immunoengineering (University of California San Diego)

Project Scientist – Breast and Hematological Tumors (Cedars-Sinai)

Postdoctoral Associate – Immune Responses (The Jackson Laboratory)

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