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. 2019 Aug 27;9:799. doi: 10.3389/fonc.2019.00799

Figure 2.

Figure 2

Defective TGFβ signaling in HNSCC increases altEJ (52). (A) TGFβ signaling suppresses miR182, which suppresses expression of BRCA1 and FOXO3. DNA damage elicits activates ATM autophosphorylation and its phosphorylation of BRCA1, which gives rise to use of HRR in S-phase. (B) In contrast, deficient TGFβ signaling, which can be caused by HPV infection, TGFβ receptor kinase inhibitors (TBRi) or SMAD4 mutations (SMAD4 mut), leads to increased miR182 that suppresses BRCA1 and FOXO3. Loss of FOXO3 inhibits ATM auto-activation, which together with decreased BRCA1, impedes HRR. This is accompanied by increased altEJ.