Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model

C Yu,Y Gong,H Zhu,M Wang,L Kong,T An,H Zhou,Y Li,J Liu

doi:10.1038/cddis.2016.199

Abstract

Star-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway. The growth of breast cancer xenografts in NOD/SCID mice was also inhibited by the doxycycline-induced Star-PAP overexpression. Furthermore, Star-PAP sensitized breast cancer cells to chemotherapy drugs both in vitro and in vivo. In mammary epithelial cells, Star-PAP knockdown partially transformed these cells and induced them to undergo epithelial–mesenchymal transition (EMT). These findings suggested that Star-PAP possesses tumor-suppressing activity and can be a valuable target for developing new cancer therapeutic strategies.

Highlights

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, with an estimated 1 676 600 new cases and 521 900 deaths according to GLOBOCAN 2012.1 Cancer cells, including breast cancer cells, usually manifest aberrant gene expression that leads to malignancy, such as sustaining proliferation, metastasis and evasion of apoptosis.[2]
To investigate whether Star-PAP involves in human breast cancer pathogenesis, we first examined the expression of Star-PAP in a panel of breast cancer cell lines
We examined the expression of StarPAP, both mRNA and protein levels, in breast cancer cells as well as clinical breast tumors, and we observed a consistent differential Star-PAP expression existing between the normal and cancerous breast condition (Figure 1)

Summary

Introduction

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, with an estimated 1 676 600 new cases and 521 900 deaths according to GLOBOCAN 2012.1 Cancer cells, including breast cancer cells, usually manifest aberrant gene expression that leads to malignancy, such as sustaining proliferation, metastasis and evasion of apoptosis.[2]. It was reported that Star-PAP inhibits the lipogenesis and the cell proliferation in osteosarcoma cells in vitro.[11] the functional role of Star-PAP in cancer development and treatment is unclear. The function of Star-PAP in human breast cancer was investigated in this study. Ectopic expression of Star-PAP inhibited the proliferation of breast cancer cells, and Star-PAP induced the mitochondrial apoptosis through regulating the expression of BIK (BCL2interacting killer). This study indicated that Star-PAP has a potential tumor-suppressing function in breast cancer and can be a valuable molecular target for breast cancer therapy and prevention

Methods

Results

Conclusion