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. 2022 Dec 5;119(50):e2217953119. doi: 10.1073/pnas.2217953119

Fig. 1.

Fig. 1.

In normal tissues, MARCO and procollagen-lysine, 2-oxoglutarate 5-dioxygenases 2 (PLOD2) are expressed in different cell types. MARCO is solely expressed in macrophages, monocytes, and dendritic cells, whereas PLOD2 is widely expressed in different cell types but not immune cells. In some TNBCs, the BRD4-driven super-enhancer activates an alternative promoter (P1) of MARCO, resulting in the transcription of a splicing variant MARCO-TST. MARCO-TST interacts with PLOD2 in TNBC and promotes PLOD2 dimerization and activation. Enhancement of PLOD2 activity can drive cancer progression by promoting collagen cross-linking. It also reduces the levels of intracellular α-KG and inhibits the degradation of HIF-1α, thereby activating the hypoxic response. Consequently, these tumors respond better to BETi.