Équipe : BMP, Niche tumorale et resistance
Responsable : Maguer-Satta Véronique
Laboratoire : UMR 5286 Centre de Recherche en Cancerologie de Lyon (LYON)
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Descriptif :
BMP, a multimodal signalling platform to drive transformation and resistance of cancer stem cells Over the past decade, our team showed in different systems that alteration of the BMPs signalling pathway and their biological effects contributes to the cancer stem cell (CSC) phenotype and their resistance to treatments. Linked to the multiple functions of BMPs in many different types of cancer, we now propose that deregulation of this pathway result from a set of alterations (such as signalling modulation through dynamic molecular complexes and BMP receptors location, abnormal stem cells functional features and biomechanical properties, microenvironment interaction and cross-regulation), characteristic to each organ/tissue may. The BMP pathway, major during embryogenesis, thus could play a central role in various aspects of carcinogenesis and constitutes a potential therapeutic target. Indeed, its deregulation is probably a common event regardless of the origin of the CSC (or tumor-initiating cell) and not clearly established in the majority of cancers. Following our demonstration of the involvement of the BMP signalling alterations in SCs and their niche in CSC of breast cancer and leukemia, we are now deciphering the impact of this pathway in early phases of transformation or resistance by including trans-disciplinary analysis in the fields of mathematic (stem cell state dynamic by mathematic modelling) and biomechanics (microfluidic, cell confinement, Brillouin 3D-imaging) and environmental pollutants (Bisphenol, Benzene, Nanoplastics). Our approach is based on the modulation of the expression of the elements of the BMP pathway and the characterization of their biological response to specific signals and context using 2D and 3D human microenvironment-like system and cell line models or primary cells from healthy donors, breast cancer and leukemic patients. We then expect to be able to decipher some key aspects of the BMP pathway to propose new strategies to efficiently prevent emergence and tumor escape by improving 1) our understanding of the origin and consequences of the deregulation of the BMP pathway in CSC and alteration of the tumor niche and 2) identifying and controlling the unique features of CSC to counteract their resistance to treatments. This will extend our knowledge of the molecular and function of BMPs in the complex, heterogenous, and dynamic integrated tumor ecosystem.
BMP, a multimodal signalling platform to drive transformation and resistance of cancer stem cells Over the past decade, our team showed in different systems that alteration of the BMPs signalling pathway and their biological effects contributes to the cancer stem cell (CSC) phenotype and their resistance to treatments. Linked to the multiple functions of BMPs in many different types of cancer, we now propose that deregulation of this pathway result from a set of alterations (such as signalling modulation through dynamic molecular complexes and BMP receptors location, abnormal stem cells functional features and biomechanical properties, microenvironment interaction and cross-regulation), characteristic to each organ/tissue may. The BMP pathway, major during embryogenesis, thus could play a central role in various aspects of carcinogenesis and constitutes a potential therapeutic target. Indeed, its deregulation is probably a common event regardless of the origin of the CSC (or tumor-initiating cell) and not clearly established in the majority of cancers. Following our demonstration of the involvement of the BMP signalling alterations in SCs and their niche in CSC of breast cancer and leukemia, we are now deciphering the impact of this pathway in early phases of transformation or resistance by including trans-disciplinary analysis in the fields of mathematic (stem cell state dynamic by mathematic modelling) and biomechanics (microfluidic, cell confinement, Brillouin 3D-imaging) and environmental pollutants (Bisphenol, Benzene, Nanoplastics). Our approach is based on the modulation of the expression of the elements of the BMP pathway and the characterization of their biological response to specific signals and context using 2D and 3D human microenvironment-like system and cell line models or primary cells from healthy donors, breast cancer and leukemic patients. We then expect to be able to decipher some key aspects of the BMP pathway to propose new strategies to efficiently prevent emergence and tumor escape by improving 1) our understanding of the origin and consequences of the deregulation of the BMP pathway in CSC and alteration of the tumor niche and 2) identifying and controlling the unique features of CSC to counteract their resistance to treatments. This will extend our knowledge of the molecular and function of BMPs in the complex, heterogenous, and dynamic integrated tumor ecosystem.
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