Stress signaling in breast cancer cells induces matrix components that promote chemoresistant metastasis.

ABSTRACT: Metastatic progression remains a major burden for cancer patients and is associated with eventual resistance to prevailing therapies such as chemotherapy. Here, we reveal how chemotherapy induces an extracellular matrix (ECM), wound healing, and stem cell network in cancer cells via the c-Jun N-terminal kinase (JNK) pathway, leading to reduced therapeutic efficacy. We find that elevated JNK activity in cancer cells is linked to poor clinical outcome in breast cancer patients and is critical for tumor initiation and metastasis in xenograft mouse models of breast cancer. We show that JNK signaling enhances expression of the ECM and stem cell niche components osteopontin, also called secreted phosphoprotein 1 (SPP1), and tenascin C (TNC), that promote lung metastasis. We demonstrate that both

SUBMITTER: Insua-Rodriguez J 

PROVIDER: S-EPMC6180299 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature