P53 mutations in triple negative breast cancer upregulate endosomal recycling of epidermal growth factor receptor (EGFR) increasing its oncogenic potency  Iuliana Shapira, Annette Lee, Reena Vora, Daniel R. Budman  Critical Reviews in Oncology / Hematology  Volume 88, Issue 2, Pages 284-292 (November 2013) DOI: 10.1016/j.critrevonc.2013.05.003 Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 1 Endosomal trafficking of EGFR and integrin alpha5 beta1 in basal like breast cancer: A mutant form of the tumor suppressor protein p53 sequesters p63 (a transcription factor and p53 family member) and blocks its transcriptional activity. Sequestration of p63 by mutant p53 blocks its anti-metastatic abilities in part by diminishing the activity of Rab7 (the molecular motor responsible for the transport of EGFR cargo to the lysosome for degradation). This mechanism enhances the potency of EGFR signaling via recycling of EGFR and integrin back to the plasma membrane instead of allowing their degradation into the lysosome. An increase in EGFR and alpha5beta1 integrin signaling in the endosome and at the cell surface boosts the phosphorylation and activation of the Akt kinase and upregulates the invasive metastatic potential of these basal like breast cancer cells. Critical Reviews in Oncology / Hematology 2013 88, 284-292DOI: (10.1016/j.critrevonc.2013.05.003) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions

Fig. 2 The endosomal cycle: illustrated in blue arrows are epidermal growth factor receptors recycling pathways and in pink are secretory pathways. [95–97]. Critical Reviews in Oncology / Hematology 2013 88, 284-292DOI: (10.1016/j.critrevonc.2013.05.003) Copyright © 2013 Elsevier Ireland Ltd Terms and Conditions