Genomic profiling of B-cell leukemia and lymphoma has put BTG1 and BTG2 in the spotlight, since both genes are frequently deleted or mutated in these malignancies, pointing towards a role as tumor suppressors.
Taken together, TIS21 attenuated Doxo-induced cancer cell senescence by inhibiting linear actin nucleation via Nox4-ROS-ABI2-DRF signal cascade, implying that expression of TIS21 overcomes resistance of senescent cells to cancer chemotherapy via inhibiting linear actin nucleation.
Furthermore, Sp1-mediated Nox4 transcription was downregulated by TIS21(/BTG2/Pc3)-Akt1 signals, leading to the inhibition of cancer cell invasion via F-actin remodeling by mDia genes.
In conclusion, our study reveals that BTG2 negatively regulated cancer cell migration by inhibiting Src activity through downregulation of ROS generation in mitochondria.