Targeting oncogenic MAGEA6 sensitizes triple negative breast cancer to doxorubicin through its autophagy and ferroptosis by stabling AMPKα1.

Melanoma-associated antigen A6 (MAGEA6) is well known to have oncogenic activity, but the underlying mechanisms by which it regulates tumor progression and chemo-resistance, especially in triple-negative breast cancer (TNBC), have been unknown. In the study, the differential expression genes (DEGs) in TNBC tumor tissues and TNBC-resistant tumor tissues were analyzed based on TCGA and GEO datasets. MAGEA6, as the most significantly expressed gene, was analyzed by RT-qPCR, western blotting and immunohistochemistry assay in TNBC cell lines and tumor tissues.

Treatment with eFT-508 increases chemosensitivity in breast cancer cells by modulating the tumor microenvironment.

Background: Patients with triple-negative breast cancer (TNBC) are better responders to neoadjuvant chemotherapy; however, they are poor in the durability of response with decreased overall and progression-free survival.

Methods: Given that significant improvements have been reported with PD-L1-PD-1 blockade in different cancers, we evaluated the in vitro and in vivo effectiveness of Tomivosertib (eFT-508), an anthracycline, adriamycin, and MNK1/2 inhibitor, which has been previously shown to inhibit translation of PD-L1 in mice model of liver cancer, alone or in combination using BC cell lines and an orthotopic xenograft mice model using the TNBC cell line MDA-MB-231.

Results: Within the context of The Cancer Genome Atlas (TCGA) dataset, expression of CD274 mRNA, which encodes programmed death-ligand 1 (PD-L1), was found to be significantly overexpressed in TNBC patients compared to patients with HER2 + or luminal breast cancer (BC).

PCBP1-mediated regulation of WNT signaling is critical for breast tumorigenesis.

Loss of expression or protein kinase B (Akt1)-mediated post-translational modification of the RNA binding protein Poly r(C) binding protein 1 (PCBP1) is closely related to metastatic advancement of breast cancer. However, the role of PCBP1 in tumorigenesis is not completely defined. Using a xenograft orthotopic model of breast tumorigenesis (4T1-Pcbp1), we show here that PCBP1 knockdown-induced tumorigenesis is inhibited by activation of the WNT signaling via treating with the glycogen synthase kinase 3 beta inhibitor TWS119, but not the Akt2/Akt3 inhibitor GSK690693.

Anderson Insulators in Self-Assembled Gold Nanoparticles Thin Films: Single Electron Hopping between Charge Puddles Originated from Disorder.

The Anderson insulating states in Au nanoparticle assembly are identified and studied under the application of magnetic fields and gate voltages. When the inter-nanoparticle tunneling resistance is smaller than the quantum resistance, the system showing zero Mott gap can be insulating at very low temperature. In contrast to Mott insulators, Anderson insulators exhibit great negative magnetoresistance, inferring charge delocalization in a strong magnetic field.

Nearly isotropic piezoresistive response due to charge detour conduction in nanoparticle thin films.

Piezoresistive responses of nanoparticle thin-film strain sensors on flexible polyimide substrates were studied. Disordered interparticle tunneling introduces microscopic detour of charge conduction so as to reduce gauge factors. The disorder also results in large resistance change when current flows in the direction perpendicular to a unidirectional strain, reducing response anisotropy.

Identification of Mott insulators and Anderson insulators in self-assembled gold nanoparticles thin films.

How the interparticle tunnelling affects the charge conduction of self-assembled gold nanoparticles is studied by three means: tuning the tunnel barrier width by different molecule modification and by substrate bending, and tuning the barrier height by high-dose electron beam exposure. All approaches indicate that the metal-Mott insulator transition is governed predominantly by the interparticle coupling strength, which can be quantified by the room temperature sheet resistance. The Hubbard gap, following the prediction of quantum fluctuation theory, reduces to zero rapidly as the sheet resistance decreases to the quantum resistance.