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Mig6 is a sensor of EGF receptor inactivation that directly activates c-Abl to induce apoptosis during epithelial homeostasis

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Estrogen receptor signaling in the human breast epithelium

Céline Berthe Constantin

Breast cancer is the most diagnosed malignancy in women worldwide, making effective prevention strategies crucial. Hormonal contraceptives, consisting of a synthetic progesterone receptor agonist alone or in combination with an estrogen, are used by millio ...

EPFL2022

Differential impact of TGF beta/SMAD signaling activity elicited by Activin A and Nodal on endoderm differentiation of epiblast stem cells

Pierre Osteil

Allocation of cells to an endodermal fate in the gastrulating embryo is driven by Nodal signaling and consequent activation of TGF beta pathway. In vitro methodologies striving to recapitulate the process of endoderm differentiation, however, use TGF beta ...

WILEY2022

Structure and regulation of the myotonic dystrophy kinase-related Cdc42-binding kinase

Charlotte Julie Caroline Gehin

Protein kinases of the dystonia myotonica protein kinase (DMPK) family are critical regulators of actomyosin contractility in cells. The DMPK kinase MRCK1 is required for the activation of myosin, leading to the develop-ment of cortical tension, apical con ...

CELL PRESS2023

Regulation and function of a hemicleaved Activin-A processing intermediate in melanoma

Manon Bulliard

Activin-A is a Transforming Growth Factor-B (TGFB)-related cytokine that regulates various biological processes including cell proliferation and differentiation through autocrine, paracrine or endocrine signaling. Activin-A expression is upregulated in mul ...

EPFL2023

Apelin-driven endothelial cell migration sustains intestinal progenitor cells and tumor growth

Michele De Palma, Mauro Delorenzi, Mario Leonardo Squadrito, Nadine Fournier, Sina Nassiri

Stem and progenitor cells residing in the intestinal crypts drive the majority of colorectal cancers (CRCs), yet vascular contribution to this niche remains largely unexplored. Vascular endothelial growth factor A (VEGFA) is a key driver of physiological a ...

Springernature2022

CDN1163, an activator of sarco/endoplasmic reticulum Ca2+ ATPase, up-regulates mitochondrial functions and protects against lipotoxicity in pancreatic β-cells

Andreas Wiederkehr

Background and Purpose: High levels of Ca2+ in the endoplasmic reticulum (ER), established by the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA), are required for protein folding and cell signalling. Excessive ER Ca2+ release or decreased SERCA activity i ...

2023

Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1(T315I) and BCR-ABL1(T315I-E255K)

Oliver Hantschel

Resistance remains the major clinical challenge for the therapy of Philadelphia chromosome-positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common "gatekeeper" mutation T315I ...

SPRINGER2021

Bioengineering human mini-intestines with in vivo-like complexity and function

Olga Mitrofanova

Biological research heavily relies on the use of animal models, which has made it difficult to answer specific questions about human biology and disease. However, with the advent of human organoids - miniature versions of tissues generated in 3D human stem ...

EPFL2023

Phosphoproteomics and morphology of stored human red blood cells treated by protein tyrosine phosphatases inhibitor

Gerardo Turcatti, Benjamin Rappaz, Romain Hamelin, Florence Armand

The process of protein phosphorylation is involved in numerous cell functions. In particular, phosphotyrosine (pY) has been reported to play a role in red blood cell (RBC) functions, including the cytoskeleton organization. During their storage before tran ...

2023

Elucidating and modulating regulatory pathways so as to reprogram the immunosuppressive tumor microenvironment for therapeutic benefit

Agnieszka Alicja Chryplewicz

Glioblastoma (GBM) is the most frequent and highly malignant form of brain cancer. New therapeutic regimens are urgently needed as GBM patients present with a minimal response to currently-approved therapies. The goal of this project is to identify new the ...

EPFL2023

Single-cell lipidomics reveals a role for cell-to-cell sphingolipid heterogeneity in fibroblast activation

Laura Capolupo

Cell-to-cell variability plays a key role in tissue patterning by setting initial asymmetry that primes cell fate decisions. Fluctuations in the activity of regulatory molecules can commit individual cells to divergent differentiation pathways, and cell-to ...

EPFL2021

Metabolic and transcriptomic profiles of glioblastoma invasion revealed by comparisons between patients and corresponding orthotopic xenografts in mice

Cristina Ramona Cudalbu Moldovan, Lijing Xin, Mario Gaetano Lepore, Marta Lai

The invasive behavior of glioblastoma, the most aggressive primary brain tumor, is considered highly relevant for tumor recurrence. However, the invasion zone is difficult to visualize by Magnetic Resonance Imaging (MRI) and is protected by the blood brain ...

2021

Multitarget-Directed Gallium(III) Tris(acyl-pyrazolonate) Complexes Induce Ferroptosis in Cancer Cells via Dysregulation of Cell Redox Homeostasis and Inhibition of the Mevalonate Pathway

Farzaneh Fadaei Tirani

A series of Ga(Q(n))(3) coordination compounds have been synthesized, where HQ(n) is 1-phenyl-3-methyl-4-RC(=O)-pyrazolo-5-one. The complexes have been characterized through analytical data, NMR and IR spectroscopy, ESI mass spectrometry, elemental analysi ...

AMER CHEMICAL SOC2023

Discovery and Development of Hyperthermia-Enhanced Treatments for Malignant Skin and Uveal Melanomas

Mouna Hadiji

Melanomas are among the deadliest cancers, with a high predisposition to metastasis and a bad prognosis in their late stages. The effectiveness of current therapeutic regimens remains suboptimal, and despite initial successes, treatment resistance emerges ...

EPFL2023

Overcoming microenvironmental resistance to PD-1 blockade in genetically engineered lung cancer models

Michele De Palma, Etienne Meylan, Nadine Fournier, Chiara Cianciaruso, Sina Nassiri, Amaia Martinez Usatorre, Ece Kadioglu, Ioanna Keklikoglou, Gael Luis Boivin, Alan Nicolas Thierry Guichard, Bruno Torchia

Immune checkpoint blockade (ICB) with PD-1 or PD-L1 antibodies has been approved for the treatment of nonsmall cell lung cancer (NSCLC). However, only a minority of patients respond, and sustained remissions are rare. Both chemotherapy and antiangiogenic d ...

AMER ASSOC ADVANCEMENT SCIENCE2021

A secreted factor NimrodB4 promotes the elimination of apoptotic corpses by phagocytes in Drosophila

Bruno Lemaitre, Florent François Masson, Samuel Rommelaere, Elodie Julie Virginie Ramond, Bianca Marie Petrignani

Programmed cell death plays a fundamental role in development and tissue homeostasis. Professional and non-professional phagocytes achieve the proper recognition, uptake, and degradation of apoptotic cells, a process called efferocytosis. Failure in effero ...

2021

Reprogramming G Protein-Coupled Receptor Structure, Function And Signaling By Computational Design

Dániel Kéri

G protein-coupled receptors (GPCRs) are 7-transmembrane alpha-helical integral membrane proteins on which cells heavily rely to receive information regarding their external environment. These receptors are able to transfer information to intracellular down ...

EPFL2021

Influenza A viruses use multivalent sialic acid clusters for cell binding and receptor activation

Suliana Manley, Christian Sieben

Influenza A virus (IAV) binds its host cell using the major viral surface protein hemagglutinin (HA). HA recognizes sialic acid, a plasma membrane glycan that functions as the specific primary attachment factor (AF). Since sialic acid alone cannot fulfill ...

2020