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. 2011 Dec 12;33(2):250–260. doi: 10.1038/aps.2011.163

Figure 5.

Figure 5

TOB1 was involved in regulation of tumor growth and metastasis via the PI3K/PTEN signaling pathway. The binding of EGF to the corresponding EGF receptors activates PI3K and downstream signaling pathways, including Akt and ERK/p38 MAPK, leading to the activation of NF-κB gene expression. Consequently, the expression of cyclin D1 and MMPs are increased, resulting in the promotion of lung cancer tumorigenesis and metastasis. Despite its activation of NF-κB, Akt can also inhibit β-catenin expression, which plays an important role in mediating cellular adhesion together with α- and γ-catenin/cadherin complexes. In the present study, TOB1 was identified as a negative regulator of EGFR expression, increasing the expression of PTEN, which functions as the central negative regulator of the PI3K/AKT pathway in controlling tumorigenesis and metastasis. The protein–protein interaction between TOB1 and PTEN was detected for the first time in cultured lung cancer cells; hence, TOB1 may be a regulator of PTEN activity.