PIK3CA and neoplasm: More recently, we found that while mice lacking Usp11 displayed increased susceptibility to PTEN-dependent tumor initiation, growth and metastasis, USP11 antagonized PI3K/AKT activity by reversing polyubiquitination and subsequently upregulating PTEN expression both in vitro and in vivo43, revealing it to be both an X-linked tumor suppressor and an important physiological PTEN deubiquitinase (Fig. 3).