Epigenetic Deregulation of Transposable Elements Links Developmental Processes and Tumorigenesis

TL;DR

This paper explores how transposable elements, normally involved in development, may contribute to cancer by causing epigenetic changes linked to dedifferentiation.

Contribution

The paper highlights a novel connection between transposable elements, developmental processes, and cancer progression through epigenetic deregulation.

Findings

Transposable elements are linked to both placental development and cancer through epigenetic mechanisms.

Cancers may repurpose developmental genes, including those derived from transposable elements, to promote invasion and metastasis.

Epigenetic reprogramming in cancer resembles early developmental states, increasing phenotypic plasticity.

Abstract

Dedifferentiation—the acquisition of an early developmental state—is a hallmark of cancer. However, the underlying mechanisms that lead to cancer-associated dedifferentiation are not fully understood. Transposable elements (TEs) are becoming increasingly recognised as important regulators of development and disease. The recruitment of TE sequences has played an important role in placental evolution, and TE-derived genes play critical roles in placental development. Although important biological differences exist between tumours and the placenta, the placenta shares certain features with tumours, including the capacity to invade surrounding tissue and modulate the maternal immune response. In this regard, TEs have been implicated in cancer development, and are documented to contribute to oncogenesis through multiple different mechanisms. Moreover, cancers reacquire an epigenetic landscape, which is reflective of early development, and which corresponds to increased phenotypic plasticity, including facilitating the activation of early developmental genes. Many cancers can repurpose developmental genes, including TE-associated genes, which may contribute to pathways involved in invasion and metastasis. Determining whether TE activation is a consequence of broader epigenetic reprogramming or actively contributes to dedifferentiation will be important for understanding cancer biology and may facilitate improvements in cancer diagnosis and treatment.

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