Anoikis is a form of apoptosis which occurs when anchorage-dependent cells either show loss of adhesion or inappropriate adhesion. Only a few cancer cells that detach from the primary site of the tumor acquire the ability to resist anoikis and form metastasis. The mechanism underlying the resistance of colorectal cancer (CRC) cells to anoikis remains unclear. Interleukin-8 (alternatively known as CXCL8) is associated with CRC angiogenesis and progression. Here, we found that a high abundance of CXCL8 or TOPIC strongly correlated with poor overall and disease-free survival of 186 patients with CRC. A combination of high CXCL8 and high TOPIC expressions had the worst prognosis. We showed that CXCL8 expression was negatively correlated with anoikis in CRC cells. CXCL8 treatment enhanced the resistance of CRC cells to apoptosis, which was accompanied by the increase of TOPIC, and the activation of AICT and ERK. Moreover, we demonstrated that the inhibition of either ERK or AKT by specific chemical inhibitors attenuated the CXCL8-mediated resistance to anoikis. Treatment with AKT inhibitor abolished the effects of CXCL8 on TOPIC expression, suggesting that TOPIC was downstream of AKT in the process of anoikis. Taken together, we demonstrated that CXCL8 is strongly implicated in the resistance of CRC cells to anoikis, and that the AKT, TOPIC and ERK pathway may be a potential therapeutic target for CRC. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
[1]Kunming Med Univ, Affiliated Hosp 3, Colorectal Canc Clin Res Ctr, Kunming 650118, Peoples R China.
[2]Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Mol Oncol Lab, Shanghai 200438, Peoples R China.
[3]First Peoples Hosp Qujing, Med Oncol, Qujing 655000, Peoples R China.
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