FOXM1 Oncogene Interferes with Stem Cell Differentiation and Promotes Cancer-Like Cell Behavior

The role of the FOXM1 oncogene in initiation of cancer-like cell transformations has been defined using a three-dimensional cell culture system.

Investigators at Queen Mary University (London, United Kingdom) worked with cultures of human keratinocytes with stem/progenitor cell properties growing in a functional three-dimensional organotypic epithelial tissue regeneration system. Use of this three-dimensional tissue culture system allowed researchers to perform experiments on manipulated human cells without provoking ethical issues associated with human or animal subjects.

They reported in the November 9, 2010, online edition of the journal Cancer Research that aberrant upregulation of FOXM1 in adult human epithelial stem cells induced a precancer phenotype, a condition similar to human hyperplasia. They showed that excessive expression of FOXM1 exploited the inherent self-renewal proliferation potential of stem cells by interfering with the differentiation pathway, thereby expanding the progenitor cell compartment. It was therefore hypothesized that FOXM1 induced cancer initiation through stem/progenitor cell expansion.

Senior author Dr. Muy-Tek Teh, lecturer in head and neck cancer at Queen Mary University, said, "Now we know that FOXM1 plays a key role in cancer initiation we aim to translate our basic findings into clinically useful molecular diagnostic tests to detect cancer growth at early stages. Furthermore, understanding the origin of cancer initiation may unveil new research opportunities for finding effective antitumor drugs that stop or prevent cancer at its earliest incipient stage.”

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