H2020Individual fellowship2017–2019

BCSC-ST · Breast cancer stem-like cells specific vulnerabilities: focus in HER2 over-expression and protein glycosylation

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration: 2017-03-01 → 2019-02-28
EU contribution: €195,455
Participants: 1
Scheme: MSCA-IF

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Results in brief

Breast cancer stem-like cells specific vulnerabilities: focus in HER2 over-expression and protein glycosylation

New therapies for breast cancer are based on the molecular differences between cancerous and normal cells and have an increased efficiency and less secondary effects. Unfortunately, a significant number of tumours do not respond to the current treatments. A small population of cells that display stem cell characteristics has been described (Breast Cancer Stem-like Cells; BCSCs) and linked to tumour progression, resistance to treatment and metastasis. Novel therapeutic approaches propose the use of stem cell targeting agents in combination with traditional chemotherapy. However, selective targeting of BCSCs is still challenging, as they are very similar to normal stem cells. We have worked in two of their characteristics: 1. HER2 Overexpression Our previous results showed that the axis IL6-STAT3-S100A8/9 is activated and essentaial in breast tumours that overexpress HER2. We analysed if the axis is activated in BCSC opening the door to a treatment that specifically targets this population. 2. Altered protein glycosylation BCSC show alterations in the glycosylation patterns of their proteins. The activity of some of the enzymes that modulate protein glycosylation is necessary to maintain the stem compartment of the breast tumours. We have generated the first CRISPR library against every protein glycosylation gene annotated. This is an important tool that could be of the interest of multiple scientists worldwide and we will use it to determine which of these enzymes are essential for BCSC to survive. The overall objective of the project is to identify new molecules in BCSC that can be targeted therapeutically, with the final goal of increasing the survival of breast cancer patients and improving their quality of life.

Data: CORDIS, © European Union

Project objective

Breast cancer is the most common cause of female cancer death in Europe, hence it is urgent finding alternative treatments. A small population of cells that display stem cell characteristics has been described in breast cancer (BCSC) and linked to tumour progression, resistance to treatment and metastasis. New therapeutic approaches propose the use of stem cell targeting agents in combination with traditional chemotherapy. However, selective targeting of BCSC is still challenging as they are very similar to normal stem cells. Here, I propose to probe two characteristics that may be specific of BCSC: HER2 over-expression and altered protein glycosylation. I will use state-of-the-art technologies including the standardization of a new protocol to isolate Circulating Tumour Cells (CTCs) from blood, and the generation of a library of CRISPRs targeting all the genes related with protein glycosylation. After six years of postdoctoral stage in New York, I have wide experience in RNAi screens valuable for the library development. Supervised by Prof. Elliott at Newcastle University, I aim to learn the insights of protein glycosylation in cancer. The identification of BCSC specific vulnerabilities has important clinical implications as they represent outstanding candidates for new targeted therapies. Importantly, HER2 and protein glycosylation are mainly located in the surface of the cells, being accessible to targeting agents. The accomplishment of the proposal will contribute to my development as an independent researcher since I will: 1) gain knowledge in BCSC and protein glycosylation, fields with multiple functional implications; 2) generate data to use in my future projects, including a list of targeted therapies candidates; 3) standardize a method for isolating CTCs to further study breast cancer metastasis; 4) learn to use CRISPR libraries and generate a library with multiple applications; and 5) be trained and guided in the transition to a full autonomous position.

Original text from CORDIS.

Participants

UNIVERSITY OF NEWCASTLE UPON TYNE · Newcastle Upon TyneCoordinatorUnited Kingdom

BCSC-ST · Breast cancer stem-like cells specific vulnerabilities: focus in HER2 over-expression and protein glycosylation

Results in brief

Breast cancer stem-like cells specific vulnerabilities: focus in HER2 over-expression and protein glycosylation

Project objective

Participants

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