Isidro Sánchez‐García

Universidad de Salamanca

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Carolina Vicente‐Dueñas

Instituto de Investigación Biomédica de Salamanca

110

César Cobaleda

Centro de Biología Molecular Severo Ochoa

Inés González‐Herrero

Centro de Investigación del Cáncer

ÓB

Óscar Blanco

Instituto de Investigación Biomédica de Salamanca

AÓ

Alberto Órfão

Centro de Investigación Biomédica en Red de Cáncer

Diego Alonso‐López

Centro de Investigación del Cáncer

Javier De Las Rivas

Centro de Investigación del Cáncer

Arndt Borkhardt

Deutschen Konsortium für Translationale Krebsforschung

Julia Hauer

Technical University of Munich

Idoia García‐Ramírez

Universidad de Salamanca

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Universidad de Salamanca

105

Block Center

101

Instituto de Investigación Biomédica de Salamanca

Centro de Investigación del Cáncer

Consejo Superior de Investigaciones Científicas

Centro de Investigación Biomédica en Red de Cáncer

Universidad de Navarra

Instituto de Salud Carlos III

Stanford University

Complejo Hospitalario de Salamanca

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Cancer induction by restriction of oncogene expression to the stem cell compartment This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.Thislicensedoesnot permit commercial exploitation without specific permission.

Carolina Meloni Vicente Alberto Órfão Miguel Á. Piris Isidro Sánchez‐García

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Expression (computer science)

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Players in human liposarcoma: JUN joins the cast

Cancer Biology & Therapy (2008)

César Cobaleda Rafael Jiménez Isidro Sánchez‐García

AbstractCommentary to:Involvement of c-jun in human liposarcoma growth: supporting data from clinical immunohistochemistry and DNAzyme efficacy Crispin R. Dass, Stuart J. Galloway, Jonathan C. M. Clark, Levon M. Khachigian, Peter F. M. Choong

10.4161/cbt.7.8.6582

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Citations (3)

Back to the beginning: The initiation of cancer

BioEssays (2013)

César Cobaleda Isidro Sánchez‐García

It is accepted that cancer results from the accumulation of mutations in genes controlling cell birth or cell death. Also, the microenvironment, including stromal and vascular endothelial cells, is important for the growth and persistence of the cancer cell. This entire constellation of the abnormal molecular biology of cancer cells and their microenvironment is the signature of cancer. However, we still do not understand the mechanisms leading to the origin of cancer cells sufficiently well to have an impact on cancer mortality. The most critical point of cancer development is the transition from a normal target cell to a cancer cell. However, the mechanisms establishing tumor cellular identity, which play an essential role in allowing cancers to arise, have received little attention. Recently, it has been hypothesized that cancer cells are cellular states arising as a result of external perturbations, implying that mutation would not be a direct cause for cancer origin, and that generation of cancer cells would be strongly dependent on cell-cell interactions and environmental variation 1. From this perspective, there are three key questions for understanding the cancer initiation process. (1) What are the cues instructing a target cell to switch from a normal to a cancerous fate? (2) What is the molecular nature of the cancer cell switch? (3) When, during normal cell development, does this switch take place? This last question is critical because, to find the players of the normal/cancer switch mechanism, one has to know when/where to look. The mechanisms initiating cancer must integrate developmental cues (different between cancer types) with the universal requirements for the creation of a tumor mass. Although it is generally believed that the decision to become a cancer cell must be made once the normal cell has adopted a cell fate compromise in the majority of cancers, recent data suggest that this timing of cancer initiation is not a universal feature shared by many oncogenes. Actually, several recent papers have found that oncogenes contribute to cancer development not only by inducing proliferation, but mainly via developmental reprogramming of the epigenome 2-5. Indeed, using stem-cell restricted transgenic expression systems, it has been shown that the expression of the oncogene in the reprogramming-prone stem/progenitor cells is capable of programming the development of all the cells that compose the tumor mass. Overall, these results not only highlight a previously unrecognized role for oncogenes in cancer, but also provide evidence for a previously unmodeled process for tumorigenesis in which the programming of the malignant phenotype has already taken place at the stem cell stage, thus uncovering a new role for oncogenes in the timing of cancer initiation. In this context, mutations that activate oncogenes would have a driving role in the reprogramming process, but may act as passenger mutations (or have a secondary, different role) thereafter. These findings lead to new questions. First, is the decision to initiate cancer made at one time point during the differentiation process, or are a series of consecutive decisions required to switch to a cancer-cell fate? and, are all these decisions cell-autonomous? What is the nature of the (epi)genetic pathway downstream from the cancer-specific initiation gene defect(s)? If we learn how to stop cancer development by manipulating the cancer-initiation program then, someday, understanding the initiation of cancer will also be useful for cancer therapy.

10.1002/bies.201300024

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Editorial: Epigenetic Reprogramming and Cancer Development Volume II

Frontiers in Cell and Developmental Biology (2022)

Isidro Sánchez‐García Carolina Vicente‐Dueñas G. E. Brown

EDITORIAL article Front. Cell Dev. Biol., 05 January 2022Sec. Molecular and Cellular Oncology Volume 9 - 2021 | https://doi.org/10.3389/fcell.2021.823503

Reprogramming

Epigenesis

10.3389/fcell.2021.823503

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Citations (2)

Redox Regulation of in Vitro DNA-binding Activity by the Homeodomain of the Isl-1 Protein

Journal of Molecular Biology (1993)

Isidro Sánchez‐García Terence H. Rabbitts

10.1006/jmbi.1993.1343

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Citations (13)

LMO2 Facilitates Synthetic Lethality after PARP Inhibition (PARPi) in Diffuse Large B-Cell Lymphoma (DLBCL)

Blood (2018)

Ramiro E. Verdún Salma Parvin Ariel Ramirez Labrada Gabriel E. Santiago Cortizas M Elena

10.1182/blood-2018-99-110825

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Fat-specific FUS-DDIT3-transgenic mice establish PPAR inactivation is required to liposarcoma development

Carcinogenesis (2007)

Pedro A. Pérez–Mancera Carolina Vicente‐Dueñas Inés González‐Herrero Manuel Sánchez‐Martín T. Flores-Corral

FUS-DDIT3 is a chimeric oncogene generated by the most common chromosomal translocation t(12;16)(q13;p11) associated to liposarcomas. The application of transgenic methods and the use of primary mesenchymal progenitor cells to the study of this sarcoma-associated FUS-DDIT3 gene fusion have provided insights into their in vivo functions and suggested mechanisms by which lineage selection may be achieved. These studies indicate that FUS-DDIT3 contributes to differentiation arrest acting at a point in the adipocyte differentiation process after induction of peroxisome proliferator-activated receptor γ (PPARγ) expression. To test this idea within a living mouse, we generated mice expressing FUS-DDIT3 within aP2-positive cells, because aP2 is a downstream target of PPARγ expressed at the immature adipocyte stage. Here, we report that FUS-DDIT3 expression was successfully induced at the aP2 stage of differentiation both in vivo and in vitro . aP2-FUS-DDIT3 mice do not develop liposarcomas and exhibit an increase in white adipose tissue size. Consistent with in vivo data, mouse embryonic fibroblasts (MEFs) obtained from aP2-FUS-DDIT3 mice not only were capable of terminal differentiation but also showed an increased capacity for adipogenesis in vitro compared with wild-type MEFs. Taken together, this study provides genetic evidence that the presence of FUS-DDIT3 in an aP2-positive cell is not enough to cause liposarcoma development and establishes that PPARγ inactivation is required for liposarcoma development.

Myxoid liposarcoma

10.1093/carcin/bgm107

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The Making of Leukemia

International Journal of Molecular Sciences (2018)

Inés González‐Herrero Guillermo Rodríguez-Hernández Andrea Luengas-Martínez Marta Isidro-Hernández Rafael Jiménez

Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell. This driving of cancer by a malignant epigenetic stem cell rewiring is, however, not exclusive of the hematopoietic system, but rather represents a common tumoral mechanism that is also at work in epithelial tumors. Tumoral epigenetic reprogramming is therefore a new type of interaction between genes and their target cells, in which the action of the oncogene modifies the epigenome to prime leukemia development by establishing a new pathological tumoral cellular identity. This reprogramming may remain latent until it is triggered by either endogenous or environmental stimuli. This new view on the making of leukemia not only reveals a novel function for oncogenes, but also provides evidence for a previously unconsidered model of leukemogenesis, in which the programming of the leukemia cellular identity has already occurred at the level of stem cells, therefore showing a role for oncogenes in the timing of leukemia initiation.

Reprogramming

Epigenome

10.3390/ijms19051494

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Citations (14)

How tumour cell identity is established?

Seminars in Cancer Biology (2015)

Isidro Sánchez‐García

10.1016/j.semcancer.2015.04.004

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Childhood leukemia prevention within reach