Although the relation of C3G and human cancer is controversial, an increase in C3G expression is observed in human small cell carcinoma [197], and a Crk-C3G-Rap1 pathway leading to B-RAF and Erk activation is involved in transformation downstream of Ret in papillary thyroid carcinoma [124]. Here, RAPGEF1 is linked to thyroid gland papillary carcinoma.