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Figure 8 | Breast Cancer Research

Figure 8

From: Cell-extrinsic consequences of epithelial stress: activation of protumorigenic tissue phenotypes

Figure 8

Stress-elicited extrinsic phenotypes (SEEPs). In human mammary epithelial cells with an intact p16/Rb pathway (HMEC, green cells), DNA damage (or telomere malfunction) causes cell-cycle arrest and is self-limiting. In contrast, the same type of damage in human mammary epithelial cells with a compromised p16/Rb pathway (vHMEC, red cells) results in the activin A-dependent induction of COX-2 and continued cell proliferation [5]. Activin A can drive increased COX-2 expression in adjacent epithelial cells [5] and fibroblasts (tan cells; current work) via paracrine signaling. Fibroblasts adjacent to epithelial cells with telomere malfunction, or exposed to activin A or PGE2, upregulate a number of genes to induce cell-extrinsic phenotypes associated with a protumorigenic microenvironment, as shown [10, 16]. Collectively, these factors can alter the extracellular matrix, induce angiogenesis, increase immune cell influx, drive cell proliferation, damage DNA, facilitate the switch to anaerobic metabolism, and promote cell motility [4, 14, 17, 22, 23, 26, 61–63].

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