CD36 promotes the epithelial\u2013mesenchymal transition and metastasis in cervical cancer by interacting with TGF-\u03b2

Min Deng,Shuguang Liu,Ling Long,Linying Xie,Youjian Zhou,Chao Zeng,Hongmei Ma,Xiaodong Cai

doi:10.1186/s12967-019-2098-6

Abstract

BackgroundAccumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. However, there are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer.MethodsUsing immunohistochemistry, we analyzed 133 cervical cancer samples for CD36 protein expression levels, and then investigated the correlation between changes in its expression and clinicopathologic parameters. The effect of CD36 expression on the epithelial–mesenchymal transition (EMT) in cervical cancer cells was evaluated by Western immunoblotting analysis. In vitro invasion and in vivo metastasis assays were also used to evaluate the role of CD36 in cervical cancer metastasis.ResultsIn the present study, we confirmed that CD36 was highly expressed in cervical cancer samples relative to normal cervical tissues. Moreover, overexpression of CD36 promoted invasiveness and metastasis of cervical cancer cells in vitro and in vivo, while CD36 knockdown suppressed proliferation, migration, and invasiveness. We demonstrated that TGF-β treatment attenuated E-cadherin expression and enhanced the expression levels of CD36, vimentin, slug, snail, and twist in si-SiHa, si-HeLa, and C33a–CD36 cells, suggesting that TGF-β synergized with CD36 on EMT via active CD36 expression. We also observed that the expression levels of TGF-β in si-SiHa cells and si-HeLa cells were down-regulated, whereas the expression levels of TGF-β were up-regulated in C33a–CD36 cells. These results imply that CD36 and TGF-β interact with each other to promote the EMT in cervical cancer.ConclusionsOur findings suggest that CD36 is likely to be an effective target for guiding individualized clinical therapy of cervical cancer.

Highlights

Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers
Clinical significance of CD36 expression in cervical cancer After investigating the expression levels of CD36 in 133 cases of cervical cancer tissues and 47 cases of normal cervical tissues by immunohistochemistry, we found CD36 expression to be primarily located on the cell membrane or in the cytoplasm (Fig. 1a–d)
CD36 promotes cervical cancer cell proliferation, migration, and invasion, and inhibits apoptosis To further investigate the effects of CD36 on a series of biologic processes in cervical cancer cell lines, we used Western blotting analysis to detect the expression of CD36 in C33a, Hce1, HeLa, and SiHa cells

Summary

Introduction

Accumulating evidence indicates that CD36 initiates metastasis and correlates with an unfavorable prognosis in cancers. There are few reports regarding the roles of CD36 in initiation and metastasis of cervical cancer. An increasing number of studies have found that CD36 plays a vital role in the development of cancers, especially as it relates to the process of cancer metastasis. The presence of CD36 on cancer cells initiates metastasis and correlates with an unfavorable prognosis for melanoma and breast cancer, and inhibition of CD36 impairs metastasis [13]. There are currently few reports on the expression and actions of CD36 in cervical cancer. Investigation of a new molecular mechanism for CD36 in cervical cancer metastasis is critical in improving patient prognosis

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