SSBP1 Upregulation In Colorectal Cancer Regulates Mitochondrial Mass

Yongping Yang,1,* Chenxi Pan,2,* Lingyun Yu,1 Hongxia Ruan,2 Ling Chang,2,3 Jingbo Yang,4 Zihan Zheng,2 Feng Zheng,2,3 Tongjun Liu1,4 1First Bethune Hospital, Jilin University, Changchun, Jilin, People’s Republic of China; 2Dalian Key Laboratory of Immune and Metabolic Kidney Diseases, Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Nephrology, Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 4Second Bethune Hospital, Jilin University, Changchun, Jilin, People’s Republic of China*These authors contributed equally to this manuscriptCorrespondence: Tongjun LiuDepartment of Gastrointestinal Surgery, First Bethune Hospital of Jilin University, No.828 Xinmin Street, Changchun, Jilin 130021, People’s Republic of ChinaEmail tongjunliu@163.comFeng ZhengAdvanced Institute for Medical Sciences, Dalian Medical University, 9 West Section, South Road, Lushunkou District, Dalian, Liaoning 116044, People’s Republic of ChinaEmail fzheng63@163.comBackground: Colorectal cancers (CRC) are one of the most common forms of cancer seen worldwide, and also remain difficult to treat despite recent advances in chemotherapy. Although significant progress has been made in recent years towards precision medicine and mutation-guided therapy, common mechanisms that underlie tumor growth and progression remain incompletely understood.Methods: Tumor tissue and nearby unaffected tissue were collected from >15 patients at each stage of CRC, from which we generated representative proteomics profiles of three stages. Bioinformatics analysis was performed to discover common differences that may be shared between the representative profiles and across larger cohorts. Flow cytometry was then used to identify functional consequences of SSBP1 depletion in cell lines, since its expression level was consistently increased in tumor cells across all of the datasets analyzed.Results: Direct comparison of CRC tumor and unaffected tissue at each stage demonstrated that a number of proteins involved in mitochondrial function displayed significantly altered expression patterns. Depletion of SSBP1 in colon cancer cell lines was able to trigger loss of mitochondrial mass and an increase in tumor cell death, and this effect that was further accentuated in the presence of the common chemotherapy drug cisplatin.Conclusion: Mitochondrial biogenesis and maintenance may play an important part in tumor cell survival during CRC progression, and may be a useful target for directed inhibition or adjuvant targeting in the cases of cisplatin resistance.Keywords: SSBP1, colorectal cancer, proteomics