Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells

• Published in: Brazilian journal of medical and biological research Vol. 51; no. 1; p. e6472
• Main Authors: Zhang, S, Zhang, Y, Qu, J, Che, X, Fan, Y, Hou, K, Guo, T, Deng, G, Song, N, Li, C, Wan, X, Qu, X, Liu, Y
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01.01.2018; Associação Brasileira de Divulgação Científica
• Subjects: Akt; Analysis; BIOLOGY; Cancer cells; Cellular signal transduction; Cetuximab; Colon cancer; Dosage and administration; Drug resistance; Drug therapy; Exosome; MEDICINE, RESEARCH & EXPERIMENTAL; PTEN; PTEN; Colon cancer; Akt; Cetuximab; Exosome
• ISSN: 0100-879X; 1414-431X; 1414-431X
• DOI: 10.1590/1414-431X20176472

Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.