Data from Chemotherapy-Induced Collagen IV Drives Cancer Cell Motility through Activation of Src and Focal Adhesion Kinase

• DOI: 10.1158/0008-5472.c.6513865.v1
• Publication Date: 2023-03-31T21:18:03Z
• Authors: Jackson P. Fatherree; Justinne R. Guarin; Rachel A. McGinn; Stephen P. Naber; Madeleine J. Oudin
• Keywords: Triple-negative breast cancer; Taxane

<div>Abstract<p>Triple-negative breast cancer (TNBC) is the most aggressive and deadly subtype of cancer, accounting for 30,000 cases annually in United States. While there are several clinical trials ongoing to identify new agents treat TNBC, majority patients with TNBC treated anthracycline- or taxane-based chemotherapies neoadjuvant setting, followed by surgical resection adjuvant chemotherapy. many respond well this approach, as 25% will suffer local metastatic recurrence within 5 years. Understanding mechanisms that drive after chemotherapy treatment critical improving survival TNBC. It established extracellular matrix (ECM), which provides structure support tissues, a major driver tumor growth, invasion, dissemination cells distant sites. In present study, we show decellularized ECM (dECM) obtained from chemotherapy-treated mice increases motility treatment-naïve compared vehicle-treated dECM. Tandem-mass–tag proteomics revealed induce drug-specific changes composition. The basement membrane protein collagen IV was significantly upregulated Collagen drove invasion via activation Src focal adhesion kinase signaling downstream integrin α1 α2, inhibition IV–driven decreased These studies provide novel mechanism may metastasis its effects on composition.</p>Significance:<p>Cytotoxic induces significant composition ECM, inducing more invasive phenotype residual following chemotherapy.</p></div>