Dataset Information

Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo.

ABSTRACT: Human epidermal growth factor receptor?2 (HER2) is overexpressed in >20% of breast cancers. Dimerization of HER2 receptors leads to the activation of downstream signals enabling the proliferation and survival of malignant phenotypes. Owing to the high expression levels of HER2, combination therapies are currently required for the treatment of HER2+ breast cancer. Here, we designed non-toxic transformable peptides that self-assemble into micelles under aqueous conditions but, on binding to HER2 on cancer cells, transform into nanofibrils that disrupt HER2 dimerization and subsequent downstream signalling events leading to apoptosis of cancer cells. The phase transformation of peptides enables specific HER2 targeting, and inhibition of HER2 dimerization blocks the expression of proliferation and survival genes in the nucleus. We demonstrate, in mouse xenofraft models, that these transformable peptides can be used as a monotherapy in the treatment of HER2+ breast cancer.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7147967 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo.

Zhang Lu L Jing Di D Jiang Nian N Rojalin Tatu T Baehr Christopher M CM Zhang Dalin D Xiao Wenwu W Wu Yi Y Cong Zhaoqing Z Li Jian Jian JJ Li Yuanpei Y Wang Lei L Lam Kit S KS

Nature nanotechnology 20200127 2

Human epidermal growth factor receptor 2 (HER2) is overexpressed in >20% of breast cancers. Dimerization of HER2 receptors leads to the activation of downstream signals enabling the proliferation and survival of malignant phenotypes. Owing to the high expression levels of HER2, combination therapies are currently required for the treatment of HER2<sup>+</sup> breast cancer. Here, we designed non-toxic transformable peptides that self-assemble into micelles under aqueous conditions but, on bindin ...[more]

PMID: 31988501

Similar Datasets

Project description:Although most antibiotics act on cells that are actively dividing and non-dividing cells such as in microbe sporulation or cancer stem cells represent a new paradigm for the control of disease. In addition to their relevance to health, such antibiotics may promote our understanding of the relationship between the cell cycle and cell death. No antibiotic specifically acting on microbial cells arrested in their cell cycle has been identified until the present time. In this study we used an antimicrobial peptide derived from α-pheromone, IP-1, targeted against MATa Saccharomyces cerevisiae cells in order to assess its dependence on cell cycle arrest to kill cells. Analysis by flow cytometry and fluorescence microscopy of various null mutations of genes involved in biological processes activated by the pheromone pathway (the mitogen-activated protein kinase pathway, cell cycle arrest, cell proliferation, autophagy, calcium influx) showed that IP-1 requires arrest in G0/G1 in order to kill yeast cells. Isolating cells in different cell cycle phases by elutriation provided further evidence that entry into cell cycle arrest, and not into G1 phase, is necessary if our peptide is to kill yeast cells. We also describe a variant of IP-1 that does not activate the pheromone pathway and consequently does not kill yeast cells that express the pheromone's receptor; the use of this variant peptide in combination with different cell cycle inhibitors that induce cell cycle arrest independently of the pheromone pathway confirmed that it is cell cycle arrest that is required for the cell death induced by this peptide in yeast. We show that the cell death induced by IP-1 differs from that induced by α-pheromone and depends on FIG1 in a way independent of the cell cycle arrest induced by the pheromone. Thus, IP-1 is the first molecule described that specifically kills microbial cells during cell cycle arrest, a subject of interest beyond the process of mating in yeast cells. The experimental system described in this study should be useful in the study of the mechanisms at play in the communication between cell cycle arrest and cell death on other organisms, hence promoting the development of new antibiotics.

Dataset Information

Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo.

Publications

Transformable peptide nanoparticles arrest HER2 signalling and cause cancer cell death in vivo.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets