Exosomes promote cetuximab resistance via the PTEN/Akt pathway in colon cancer cells.
Braz J Med Biol Res
; 51(1): e6472, 2017 Nov 13.
Article
in En
| MEDLINE
| ID: mdl-29160412
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colonic Neoplasms
/
PTEN Phosphohydrolase
/
Proto-Oncogene Proteins c-akt
/
Exosomes
/
Cetuximab
/
Antineoplastic Agents, Immunological
Limits:
Humans
Language:
En
Journal:
Braz J Med Biol Res
Year:
2017
Document type:
Article
Affiliation country:
China