Stress-inducible gene Atf3 in the noncancer host cells contributes to chemotherapy-exacerbated breast cancer metastasis
Abstract
Chemotherapy is a double-edged sword. It is anticancer because of its cytotoxicity. Paradoxically, by increasing chemoresistance and cancer metastasis, it is also pro-cancer. However, the mechanisms underlying chemotherapy-induced procancer activities are not well understood. Here we present data that provide mechanistic explanations for the ability of paclitaxel (PTX), a frontline chemotherapeutic agent, to exacerbate metastasis in mouse models of breast cancer. Importantly, Atf3 , a stress-inducible gene, in the noncancer host cells is necessary for this PTX effect. Analyses of publicly available datasets suggest that our data from mouse models have relevance to human cancers. Thus, ATF3 links a chemotherapeutic agent—a stressor—to pro-metastatic changes in the host cells. Dampening the effect of ATF3 may improve the efficacy of chemotherapy.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Aug 07, 2017
- Source ID
- 10.1073/pnas.1700455114
Entities
People
- Justin D. Middleton
- Swati P. Jalgaonkar
- Tsonwin Hai
- Yi Seok Chang
Organizations
- Ohio State University
- United States Department of Defense