Integral membrane protein 2A inhibits cell growth in human breast cancer via enhancing autophagy induction

Zhou，Cefan1,2; Wang，Ming3; Yang，Jing4; Xiong，Hui5,6; Wang，Yefu1; Tang，Jingfeng1,2

2019-08-22

10.1186/s12964-019-0422-7

Cell Communication and Signaling   影响因子和分区

1478-811X

Background: Breast cancer is a life-threatening disease in females and the leading cause of mortality among the female population, presenting huge challenges for prognosis and treatment. ITM2A is a member of the BRICHOS superfamily, which are thought to have a chaperone function. ITM2A has been identified to related to ovarian cancer progress recently. However, the biological role of ITM2A in breast cancer remains largely unclear. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting assay and immunohistochemistry staining were used to analyzed the expression level of ITM2A. The patient overall survival versus ITM2A expression level was evaluated by Kaplan-Meier analysis. MTT assay, EdU incorporation assay and colony formation assay were used to evaluated the role of ITM2A on breast cancer cell proliferation. Autophagy was explored through autophagic flux detection using a confocal microscope and autophagic vacuoles investigation under a transmission electron microscopy (TEM). In vitro kinase assay was used to investigated the phosphorylation modification of ITM2A by HUNK. Results: Our data showed that the expression of integral membrane protein 2A (ITM2A) was significantly down-regulated in human breast cancer tissues and cell lines. Kaplan-Meier analysis indicated that patients presenting with reduced ITM2A expression exhibited poor overall survival, and expression significantly correlated with age, progesterone receptor status, TNM classification and tumor stage. ITM2A overexpression significantly inhibited the proliferation of breast cancer cells. By studying several autophagic markers and events in human breast cancer SKBR-3 cells, we further demonstrated that ITM2A is a novel positive regulator of autophagy through an mTOR-dependent manner. Moreover, we found that ITM2A was phosphorylated at T35 by HUNK, a serine/threonine kinase significantly correlated with human breast cancer overall survival and HER2-induced mammary tumorigenesis. Conclusion: Our study provided evidence that ITM2A functions as a novel prognostic marker and represents a potential therapeutic target.

Autophagy Breast cancer HUNK ITM2A Prognosis Up-regulated Neu-associated kinase

SCI

英语

其他

WOS:000483046500001

2-s2.0-85071325437

Scopus

1.State Key Laboratory of VirologyCollege of Life SciencesWuhan University,Wuhan,China
2.National 111 Center for Cellular Regulation and Molecular PharmaceuticsHubei University of Technology,Wuhan,China
3.Department of Clinical LaboratoryRenmin HospitalWuhan University,Wuhan,China
4.Robert H. Lurie Comprehensive Cancer CenterDepartment of Medicine-Division of Hematology/OncologyNorthwestern UniversityFeinberg School of Medicine,Chicago,United States
5.Department of Clinical LaboratoryHospital of Southern University of Science and Technology,Shenzhen, Guangzhou,China
6.XiLi People's Hospital,Shenzhen, Guangzhou,China

Zhou，Cefan,Wang，Ming,Yang，Jing,et al. Integral membrane protein 2A inhibits cell growth in human breast cancer via enhancing autophagy induction[J]. Cell Communication and Signaling,2019,17(1).

Zhou，Cefan,Wang，Ming,Yang，Jing,Xiong，Hui,Wang，Yefu,&Tang，Jingfeng.(2019).Integral membrane protein 2A inhibits cell growth in human breast cancer via enhancing autophagy induction.Cell Communication and Signaling,17(1).

Zhou，Cefan,et al."Integral membrane protein 2A inhibits cell growth in human breast cancer via enhancing autophagy induction".Cell Communication and Signaling 17.1(2019).