Skip to main content
Fig. 8 | Journal of Experimental & Clinical Cancer Research

Fig. 8

From: HIF-1α switches the functionality of TGF-β signaling via changing the partners of smads to drive glucose metabolic reprogramming in non-small cell lung cancer

Fig. 8

Diagram of the TGF-β functional switch driven by increased HIF-1α under hypoxia by changing Smad partners in cancer cells. HIF-1α can be ubiquitinated and rapidly degraded under normoxic conditions. TGF-β can inhibit cell proliferation by promoting p15/p21 expression through the Smad transcription factor complex. On the other hand, Smads can bind p107 and E2F4/5 to inhibit the expression of c-Myc, thus regulating the variable splicing of PKM precursor RNA. Overall, TGF-β can inhibit cell proliferation by regulating the cell cycle and reducing glycolysis under normoxia (left). HIF-1α protein is stable in the cell under hypoxia. TGF-β promotes nuclear translocation of HIF-1α and enhances its binding with p-Smad3. High expression of HIF-1α competitively binds the MH2 domain of p-Smad3, thus relieving the inhibitory effect of the Smad-p107-E2F4/5 complex on c-Myc. c-Myc inhibits the expression of p15/p21 and regulates the variable splicing of PKM precursor RNA to express more PKM2 to promote glycolysis (right). The solid line represents the new findings described in this study, and the dotted line represents the results of previous studies

Back to article page