The metastatic cascade

In order to fully understand cancer, it is also required to unveil the interactions of cancer cells among themselves and with the microenvironment (physical and cellular ) that impinge on cell motility, plasticity, transitional states such as epithelial-mesenchymal and mesenchymal-epithelial transitions ( EMT and MET ), and many other cell behaviors ( intravasation, survival in the blood and lymph stream, extravasation, adaption to peripheral niches, etc.) that cancer cells encounter all throughout the metastatic cascade. All these processes are of paramount importance to understand malignancy, metastasis, stemness, and therapeutic resistance. It is also clinically important, given that metastasis is responsible for more than 90% of cancer-associated deaths. Yet, its understanding and treatment is far from being achieved.

    • Angela Nieto | Cell plasticity in development and disease
    • Miguel Vicente-Manzanares | Biophysics of cancer and the immune response
    • Berta L. Sánchez-Laorden | Phenotypic plasticity in melanoma
    • Ignacio Casal | Mechanisms of cancer metastasis
    • Toni Celià-Terrassa| Cancer stem cells & metastasis dynamics
    • Francisco Javier Oliver Pozo | Tumor biology: Molecular mechanisms in response to DNA damage
    • Berta Casar | Transformation and metastasis
    • Daniel Lietha | Cell signalling and adhesion
    • Mario Mellado | Chemokine receptors: new targets for therapeutic intervention

CELL PLASTICITY IN DEVELOPMENT AND DISEASE

ANGELA NIETO – Instituto de Neurociencias (CSIC-UMH)

Even though great progress has been made in the last few decades in the diagnosis and treatment of cancer, metastases are still refractory to therapy and responsible for over 90% of cancer-associated deaths. After more than 20 years working on how cells escape from the primary tumor after acquiring motility and invasive properties, we still do not know how this motility program is repressed in distant organs, for cancer cells to colonize and form metastases. We now focus on identifying the cell trajectories in tumours and the signals that promote colonization in distant organs, to test them as targets in the design of improved antimetastatic therapies.

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BIOPHYSICS OF CANCER AND THE IMMUNE RESPONSE

MIGUEL VICENTE-MANZANARES – Centro de Investigación del Cáncer

Mechanics of tumor metastasis and the antitumor immune response

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PHENOTYPIC PLASTICITY IN MELANOMA

BERTA L. SÁNCHEZ-LAORDEN – Instituto de Neurociencias (CSIC-UMH)

Our lab is interested in understanding mechanisms regulating phenotypic plasticity in melanoma that underly its high aggressiveness. Our research focuses on (i) investigating the contribution of the reactivation of developmental programs to melanoma progression and (ii) elucidating microenvironmental players regulating melanoma plasticity at the metastatic niches, particularly the brain.

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MECHANISMS OF CANCER METASTASIS

IGNACIO CASAL – Centro de Investigaciones Biológicas Margarita Salas

Our group has consolidated a solid experience in the identification and characterization of novel colorectal cancer (CRC) metastasis mediators and the role of the tumor microenvironment in cancer progression. We have thoroughly characterized the functionality of many of these proteins using a multidisciplinary approach. Current lines of research include: 1) characterization of novel metastatic effectors, 2) epithelial plasticity, stemness and drug resistance and 3) metabolic reprogramming.

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CANCER STEM CELLS & METASTASIS DYNAMICS

TONI CELIÀ-TERRASSA – Instituto Hospital del Mar de Investigaciones Médicas 

The Cancer Stem Cells & Metastasis Dynamics laboratory is dedicated to study the phenotypic heterogeneity of breast cancer metastasis and the tumor immune-microenvironment. Our research philosophy is based on the discovery of new fundamental biological processes implicated in breast cancer progression, to unveil new translational avenues for clinical applications for metastatic patients. In particular, we focus on understanding the implications of the tumor cell plasticity and phenotypic heterogeneity, reflected in cancer stem cell-like populations and EMT-like phenotypes, in breast cancer metastasis immunity and immunotherapy resistance.

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TUMOR BIOLOGY: MOLECULAR MECHANISMS IN RESPONSE TO DNA DAMAGE

FRANCISCO JAVIER OLIVER POZO – Instituto de Parasitología y Biomedicina “López – Neyra” (IPBLN-CSIC)

We have been investigating the role of PARP and PARylation in tumor biology for many years. We are currently interested in the role of PARylation in vasculogenic mimicry and HIF-mediated adaptation of tumor to hypoxia.

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TRANSFORMATION AND METASTASIS

BERTA CASAR – Instituto de Biomedicina y Biotecnología de Cantabria

The Transformation and Metastasis group at IBBTEC investigates the signaling pathways involved in abnormalities during cancer and metastasis. The ultimate goal of these studies is to identify new modulators that can represent new therapeutic targets to stop metastasis and that can be directly translated into effective prevention or treatment strategies. The group has a multidisciplinary focus and works with chick embryo and mice models, organoids and 3D cultures, clinical samples and molecular and cellular biology techniques patient-derived xenografts, to translate basic research into relevant clinical results.

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CELL SIGNALLING AND ADHESION

DANIEL LIETHA – Centro de Investigaciones Biológicas Margarita Salas

We study the structure and mechanisms of how signalling and structural elements interact in integrin associated adhesion complexes (Focal Adhesions), a complex at the centre of mesenchymal cell migration and cancer invasion.

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CHEMOKINE RECEPTORS: NEW TARGETS FOR THERAPEUTIC INTERVENTION

MARIO MELLADO – Centro Nacional de Biotecnología

Our group is interested in cell migration, in particular in the signaling events triggered by chemokines. Using powerful bioimaging technologies, such as super-resolution microscopy and single particle tracking and Total Internal Reflection Fluorescence Microscopy (TIRFM), we evaluate the receptor organization and dynamics at the cell membrane as well as the ligand-mediated signaling cascade in living cells. We also screen small compounds to interfere or modulate chemokine responses.

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