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The CD44-RANK-AKT Crosstalk in Breast Cancer and Stemness

Project description

New molecular players in breast cancer

Emerging evidence indicates that the tumour microenvironment is a key player in cancer progression, supplying growth factors that support cancer cells. The glycoprotein RANKL is present in the microenvironment and interacts with the receptor RANK, which is frequently expressed by cancer cells. Funded by the Marie Skłodowska-Curie Actions programme, the BREASTCANCERSTEM project aims to investigate the RANKL signalling pathway and the crosstalk with other downstream molecules. The key objective is to determine how the pathway is implicated in the survival of cancer stem cells, metastasis, and resistance to therapy. The work will focus on breast carcinogenesis and help identify which patients will benefit from the RANKL inhibitors currently being tested in clinical trials.

Objective

Relapse and metastasis in cancer are driven by cancer stem cells (CSC) which self-renew, give rise to tumor cell heterogeneity and are more resistant to chemotherapy. The RANK signalling pathway is implicated in a number of cancers and notably in breast carcinogenesis and metastasis. Inhibition of this pathway reduces CSCs decreasing both recurrenceRelapse and metastasis in cancer are driven by cancer stem cells (CSC) which self-renew, give rise to tumor cell heterogeneity and are more resistant to chemotherapy. The RANK signalling pathway is implicated in a number of cancers and notably in breast carcinogenesis and metastasis. Inhibition of this pathway reduces CSCs decreasing both recurrence and metastasis. RANKL inhibitors are used in breast cancer clinical trials and studies focused on RANK signalling in carcinogenesis are needed to identify patients who would benefit from treatment. RANK mediates many of its effects on cell survival, migration and chemoresistance via the PI3K/AKT pathway, activation of which confers enhanced proliferation, survival, metastatic potential and resistance to therapy in cancer. AKT is a central node in PI3K signalling and AKT isoforms play important and differential roles in carcinogenesis. RANK is also regulated by CD44, a marker of stemness and a key player in cell migration, proliferation, differentiation, survival, stem cell maintenance and chemoresistance. CD44 alternative splicing plays a pivotal role in cancer development in breast and other tissues. However, the role of CD44 and AKT isoforms in cancer is not clearly defined. In this MSCA project, I will investigate the role of the CD44-RANK-AKT crosstalk in tumorigenesis and identify CD44 and AKT isoforms regulating cancer stemness, metastasis and resistance to therapy. I hypothesize that the interplay between CD44, RANK and AKT regulates cancer stemness and the metastatic potential of breast tumor cells, and specific CD44 and AKT isoforms have vital roles in this process.

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Programme(s)

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Topic(s)

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2020

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Coordinator

FUNDACION SECTOR PUBLICO ESTATAL CENTRO NACIONAL INVESTIGACIONES ONCOLOGICAS CARLOS III
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 172 932,48
Address
C MELCHOR FERNANDEZ ALMAGRO 3
28029 Madrid
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 172 932,48
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