CriptoTDGF1

Cripto is a type of epidermal growth factor–like protein that functions as a co‑receptor for several members of the TGF‑β superfamily. The gene encoding Cripto in humans is known as TDGF1 (teratocarcinoma‑derived growth factor 1). Cripto is located on chromosome 10 (10p13) and contains a single open reading frame that encodes a secreted protein of about 145 amino acids. The protein is synthesized with a signal peptide and contains a cysteine‑rich, epidermal growth factor–like domain that mediates binding to Nodal, Activin, and TGF‑β ligands.

During early mammalian development Cripto is expressed in the epiblast and the primitive streak, where it is essential for gastrulation and axis formation. In addition to its developmental roles, Cripto influences the proliferation, survival, and migration of embryonic stem cells through activation of the ALK4/5/7 receptor complex. The protein is also implicated in tumorigenesis; overexpression of Cripto has been reported in a variety of cancers, including colorectal, breast, and lung cancers, where it promotes epithelial‑mesenchymal transition and drug resistance. Cripto signals mainly through the MAPK/ERK and PI3K/AKT pathways, although its precise mode of action remains under investigation.

The protein structure has been resolved in part by NMR studies, revealing a flexible single domain that can bind to multiple partners. Cripto is considered a potential biomarker for early-stage tumors and a target for therapeutic inhibition. Ongoing research continues to elucidate its broader physiological roles and contribution to pathological conditions.