SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer | Cancer Cell International | Full Text

SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer | Cancer Cell International | Full Text



Cancer Cell International

SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer

• Pengcheng Du†View ORCID ID profile,
• Haibin Liang†,
• Xiaowei Fu†,
• Peng Wu,
• Chao Wang,
• Haimin Chen,
• Bingbing Zheng,
• Jun Zhang,
• Shuanghui Hu,
• Rengui Zeng,
• Bo Liang and
• Lu FangEmail author

†Contributed equally

Cancer Cell International201919:33

https://doi.org/10.1186/s12935-019-0746-9

©  The Author(s) 2019

• Received: 30 November 2018
• Accepted: 4 February 2019
• Published: 14 February 2019

Abstract

Background

SLC25A22, a member of mitochondrial carrier system (MCS) family encoding a mitochondrial glutamate transporter, has been reported to have vital roles in promoting proliferation and migration in cancer. Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis. We aimed to determine the expression and function of SLC25A22 in GBC.

Methods

Immunohistochemistry (IHC) staining analysis and quantitative real-time PCR (qRT-PCR) were conducted to determine the expression of SLC25A22 in GBC tissues. Human NOZ and GBC-SD cells were used to perform the experiments. The protein expression was detected by western-blot analysis. Cell viability was evaluated via CCK-8 assay and colony formation assay. Cell migration and invasion in vitro were investigated by wound healing and transwell assay. Annexin V/PI staining assay for apoptosis were measured by flow cytometry. The effect of SLC25A22 in vivo was conducted with subcutaneous xenograft.

Results

We indicated that the expression of SLC25A22 was significantly upregulated in GBC tumor tissues as well as cell lines. Downregulation of SLC25A22 inhibited GBC cell growth and proliferation in vitro and in vivo and also had an effect on metastasis of GBC cells through the EMT processes. In addition, inhibition of SLC25A22 promoted mitochondrial apoptosis via downregulating BCL-2 and upregulating cleaved PARP, Cytochrome-c, and BAX mediated by MAPK/ERK pathway.

Conclusions

Our study identified that SLC25A22 promoted development of GBC activating MAPK/ERK pathway. SLC25A22 has a potential to be used as a target for cancer diagnosis of GBC and related therapies.

Keywords

• Gallbladder cancer
• SLC25A22
• Mitochondrial apoptosis
• MAPK/ERK