Novel insights into FOXOlogy: FOXOs and their putative role in thyroid carcinogenesis

Abstract

FOXO transcription factors regulate genes directly involved in the control of cell cycle arrest, apoptosis, DNA damage repair and antioxidative defense mechanisms. Genetic FOXO alterations and inactivation of FOXOs through oncogenic signaling cascades have been identified in several human cancers and contribute to uncoordinated cellular proliferation. To date, little is known about FOXOs in the thyroid context. In this article we will first provide an introduction into the topic of forkhead transcription factors by explaining the principles of FOXO function and regulation. We will then address specific aspects of FOXO3 function in the thyroid and possible consequences of FOXO3 deregulation in thyroid malignancy. Finally, we discuss the potential role of the PI3K/Akt/FOXO3 axis for a targeted drug therapy of advanced thyroid carcinoma.

Keywords::

• drug targeting
• FOXO1
• FOXO3
• FOXO4
• PI3K/Akt signaling
• thyroid carcinogenesis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.