NK2 homeobox 1

NK2 homeobox 1 (NKX2-1), also known as thyroid transcription factor 1 (TTF-1), is a protein which in humans is encoded by the NKX2-1 gene.

Function

Thyroid transcription factor-1 (TTF-1) is a protein that regulates transcription of genes specific for the thyroid, lung, and diencephalon. It is also known as thyroid specific enhancer binding protein. It is used in anatomic pathology as a marker to determine if a tumor arises from the lung or thyroid. NKX2.1 can be induced by activin A via SMAD2 signaling in a human embryonic stem cell differentiation model.

Clinical significance

TTF-1 positive cells are found in the lung as type II pneumocytes and club cells. In the thyroid, follicular and parafollicular cells are also positive for TTF-1.

For lung cancers, adenocarcinomas are usually positive, while squamous cell carcinomas and large cell carcinomas are rarely positive. Small cell carcinomas (of any primary site) are usually positive. TTF1 is more than merely a clinical marker of lung adenocarcinoma. It plays an active role in sustaining lung cancer cells in view of the experimental observation that it is mutated in lung cancer.