TIPE1 Suppresses Growth and Metastasis of Ovarian Cancer.

Zhenyu Zhang,Xiaohui Yan,Yuhong Sun,Kangyu Wang,Minghui Chang,Hongxin Ma,Wenjuan Sun,Xianrang Song,Xingguo Song,Li Xie,Zhihua Kang

doi:10.1155/2021/5538911

Abstract

TIPE1, a newly identified member in TIPE (TNFAIP8) family, plays an important role in tumorigenesis and immune regulation, but its role in ovarian cancer, especially in tumor metastasis, remains unknown. In the current study, we aimed to reveal the protein expression spectrum of TIPE1 in normal human tissues and explored its relationship with metastasis in ovarian cancer. The results of IHC staining showed that TIPE1 protein was not only detected in cytoplasm in most human tissues but also expressed in both cytoplasm and nucleus in squamous epithelium and some epithelial-derived cells with secretory functions, such as esophagus, cervix uteri and ovary, and thyroid gland. Moreover, TIPE1 protein was downregulated in ovarian cancer tissues compared with that in the paracancerous. More importantly, TIPE1 suppressed tumorigenesis and metastasis of ovarian cancer in vitro and in vivo, as evidence shows its ability to suppress growth, colony formation, migration, and epithelial-mesenchymal transition (EMT) of ovarian cancer. Taken together, our results demonstrate the suppressor role of TIPE1 in ovarian cancer metastasis, indicating TIPE1 might be a metastasis predictor and a novel therapeutic target for ovarian cancer.

Highlights

Ovarian cancer, the most common gynecological malignancy worldwide, has lower incidence than cervical cancer and uterine body cancer; the death rate is the highest of all gynecological tumors, which seriously poses a threat to women’s lives [1]
A recent study reported that TIPE1 was decreased in tissue microarrays and inhibited proliferation through inducing apoptosis in ovarian cancer cells [13], but whether TIPE1 related to tumor metastasis was not mentioned
Considering the strongest staining of TIPE1 protein expressed in both cytoplasm and nucleus of ovary cells, we did the following research

Summary

Introduction

The most common gynecological malignancy worldwide, has lower incidence than cervical cancer and uterine body cancer; the death rate is the highest of all gynecological tumors, which seriously poses a threat to women’s lives [1]. Is is largely due to the abnormal growth and increased cell metastasis potential of ovarian cancer cells. Erefore, seeking novel molecular alterations involved in the abnormal cell growth leading to tumor progression would facilitate the realization and development of therapies for ovarian cancer. TIPE1, a newly identified member of TIPE (tumor necrosis factor-α-induced protein 8) family, was first reported to modulate necroptosis and apoptosis in 2008 [4, 5]. Our previous studies found that TIPE1 was downregulated in hepatocellular carcinoma which could induce caspase-mediated apoptosis and inhibit HCC cell growth both in vitro and in vivo [6]. A recent study reported that TIPE1 was decreased in tissue microarrays and inhibited proliferation through inducing apoptosis in ovarian cancer cells [13], but whether TIPE1 related to tumor metastasis was not mentioned

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