title: TIPE2 suppresses the tumorigenesis, growth and metastasis of breast cancer via inhibition of the AKT and p38 signaling pathways.
abstract: Breast cancer is the second leading cause of cancer‑related deaths in female patients, and the main reasons are late diagnosis, limited therapeutic options and metastasis. Therefore, development of molecular therapeutic targets for breast cancer to suppress tumorigenesis, growth and metastasis may improve the therapeutic options and be of great benefit to patients. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a novel molecule for maintaining immune homeostasis and is involved in cancer development. Previous studies have shown that TIPE2 plays a suppressive role in the development of several types of human cancers. However, its role in breast cancer is still not clear. In the present study, we detected TIPE2 expression in human breast cancer and adjacent normal tissues. The expression of TIPE2 was reduced in breast cancer tissues compared to the level in adjacent normal tissues. We then established a breast cancer cell line stably expressing TIPE2 to investigate the role of TIPE2 in breast cancer carcinogenesis. Our results showed that overexpression of TIPE2 significantly inhibited the proliferation of MDA-MB‑231 cells as detected by Cell Counting Kit-8 assay and suppressed the migration and invasion of breast cancer cells as detected by Transwell migration and invasion assays in vitro. TIPE2 also promoted cell apoptosis as detected by flow cytometry analysis. Moreover, TIPE2 inhibited the tumorigenesis of breast cancer in vivo. Mechanistically, TIPE2 inhibited the phosphorylation of AKT and p38 as detected by western blot analysis. Taken together, TIPE2 suppressed breast cancer tumorigenesis, growth and metastasis possibly via regulation of the AKT and p38 signaling pathways. The results indicate that TIPE2 may be a potential therapeutic target for breast cancer therapy.
authors: State Institute of Pharmaceutical Industry, Shanghai 201203, P.R. China.
authors: Zhenhua
authors: Z
authors: Zhang
authors: State Institute of Pharmaceutical Industry, Shanghai 201203, P.R. China.
authors: Li
authors: L
authors: Liu
authors: School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors: Chunliang
authors: C
authors: Liu
authors: State Institute of Pharmaceutical Industry, Shanghai 201203, P.R. China.
authors: Shousong
authors: S
authors: Cao
authors: School of Pharmacy, Fudan University, Shanghai 201203, P.R. China.
authors: Yizhun
authors: Y
authors: Zhu
authors: State Institute of Pharmaceutical Industry, Shanghai 201203, P.R. China.
authors: Qibing
authors: Q
authors: Mei
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D063646:Carcinogenesis / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C552057:TNFAIP8L2 protein, human