Dear Colleagues,

Cancer is still considered one of the leading causes of death worldwide due to tumour progression triggering metastatic dissemination. Although this continues to be a sad scenario, looking back at past decades, one realises that huge improvements have been made in the field of cancer research. These advances include the discovery of oncogenes in the early 1970s, genetic and epigenetic mechanisms associated with carcinogenesis, the collaboration of tumour and host cells during the metastatic process, nanotechnology, immunotherapy and cancer organoid technology development for personalised patient treatment design. Many dedicated cancer researchers have made and are making outstanding contributions to understand and fight this complex multifactorial disease.

In 1986, Miguel Quintanilla, then as a postdoc in the lab of Allan Balmain, published a seminal paper identifying a genomic mutation in a “cancer driver” gene, which has an important role in tumour development. He described the well-known A→T transversion at the second nucleotide of codon 61 of the Harvey-ras (Ha-ras) gene, which was promoted by the exposure of mouse skin to the chemical carcinogen dimethylbenz-anthracene (DMBA). Using this classical model of mouse skin chemical carcinogenesis, Miguel Quintanilla has also made other significant contributions in the field of epithelial carcinogenesis. His findings describe the anti-invasive role of the cell–cell adhesion protein E-cadherin, whose loss is associated with tumor progression (alongside Amparo Cano and Carlos Gamallo). He also performed pioneering work to find that TGF-beta acts as a stimulator of epithelial-mesenchymal transition (EMT) associated with progression to poorly differentiated carcinomas, and the identification of the TGF-beta co-receptor endoglin as a suppressor of malignancy in epithelial carcinogenesis by a mechanism involving inhibition of TGF-beta signaling. Miguel´s work has also been a driving force towards the discovery of podoplanin (PA2.26), a small mucin-type transmembrane glycoprotein, as a promoter of malignancy in epithelial cancer by a variety of strategies including EMT induction, cooperating with CD44 to stimulate directional migration, and facilitating an efficient degradation of the extracellular matrix and stabilising invadopodia (alongside Gareth E. Jones an Ester Martin-Villar).

This Special Issue of Cells focuses on the molecular mechanisms underlying carcinogenesis and tumour progression related to the pioneering work of Miguel Quintanilla. Although genomic mutations and epigenetic changes are indisputably important during carcinogenesis, Miguel´s contributions have also brought out the importance of invasion promoting factors that facilitate tumour progression through mechanisms that do not necessarily involve DNA damage. This Special Issue intends to serve as a tribute to his work, gathering original research and timely reviews that consolidate our current knowledge of molecular mechanisms underlying cancer and open new fronts in the fight against this devastating disease.

Miguel Quintanilla, born in the monumental city of Toledo (Spain), earned his bachelor’s degree in Chemistry from the Complutense University of Madrid in 1974, and his PhD in Biochemistry from the University of Valladolid in 1980. As a postdoctoral researcher, he first joined Dr. Jaime Renart's lab at the Institute of Enzymology and Molecular Pathology (now The Institute of Biomedical Research of Madrid, IIBm) of the Spanish National Research Council (CSIC), and then moved to Scotland, joining Dr. Allan Balmain's lab at the Beatson Institute for Cancer Research (Glasgow), sponsored by the European Molecular Biology Organization (EMBO) fellowship (1984–1986). In 1987, he returned to IIBm in Spain and has been there ever since, initially as Tenured Scientist, then as a Research Professor, running the Epithelial Carcinogenesis laboratory until his retirement in 2021, as professor “ad honorem”. Miguel has always been able to follow the right scientific pathway, which has always been characterised by a true love for science, hard work, sense of humour, honesty, and generosity.

Dr. Gary S. Goldberg
Dr. Ester Martín-Villar
Guest Editors

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