Potentially transcriptional mechanism of tumor-promoter KLF11 involved in both tumor cell and tumor-associated macrophage (TAMs) in breast cancer (BC) tumor environment (TME)

In tumor cells, the inhibitory effect of KLF11 in TGF-β induced growth inhibition is potentially reversed via the ER/c-Src/RAS/MAPK/ERK axis. This leads to the disruption of the SID–mSin3A interaction. This disruption inhibits the binding of the KLF11– R-SMAD-co-SMAD complex to the DNA. Therefore, the Smad7-loop is no longer regulated, which reduces TGF-β signaling and finally leads to a reduction of the tumor-suppressive actions of TGF-β. In the TAMs, KLF11 might activate the TAMs-M1 selective gene program by forming a complex with NRs,modulating the TME into a pro-inflammatory and tumoricidal TME. Therefore, when the expression of KLF11 decreases, this might lead to a decrease of TAMs-M1, which leads to a tumor-promoting effect of the TME ([Abb. 1]).

Abb. 1

Publication History

Article published online:
11 October 2022