Jing-Zhu Cao1, Gang Nie2, Hao Hu2, Xiao Zhang3, Chen-Ming Ni2, Zhi-Ping Huang4, Guang-Lei Qiao5, Liu Ouyang2. 1. Department of Endocrinology, Changhai Hospital, Navy Medical University, Shanghai, China. 2. Department of HBP Surgery, Changhai Hospital, Navy Medical University, Shanghai, China. 3. Department of Nuclear Medicine, General Hospital of Southern Theatre Command, Guangzhou, China. 4. Department of Hepatobiliary Surgery, General Hospital of Southern Theatre Command, Guangzhou, China. 5. Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract
Background: Pancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established. Methods: UBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose. Results: UBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP. Conclusions: In conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Background: Pancreatic cancer (PC) is among the most prevalent and deadliest endocrine tumors, yet the mechanisms governing its pathogenesis remain to be fully clarified. While ubiquitin-conjugating enzyme E2C (UBE2C) has been identified as an important oncogene in several cancers, its importance in PC has yet to be established. Methods: UBE2C expression in PC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR), while appropriate commercial kits were used to assess lactate production, ATP generation, and the uptake of glucose. Results: UBE2C was found to be upregulated in PC patient tumors and correlated with poorer survival outcomes. In PC cell lines, the silencing of this gene suppressed the malignant activity of cells, thus supporting its identification as an oncogene in this cancer type. Mechanistically, UBE2C was found to promote enhanced matrix metalloproteinase (MMP) protein expression via activating the PI3K-Akt pathway. Moreover, it was found to bind to the epidermal growth factor receptor (EGFR), stabilizing it and driving additional PI3K-Akt pathway activation. UBE2C knockdown in PC cells impaired their uptake of glucose and their ability to produce lactate and ATP. Conclusions: In conclusion, the results of this study support a role for UBE2C as a driver of metastatic PC progression owing to its ability to bind to EGFR and to induce signaling via the PI3K-Akt pathway. 2022 Journal of Gastrointestinal Oncology. All rights reserved.
Authors: Evan L Fogel; Safi Shahda; Kumar Sandrasegaran; John DeWitt; Jeffrey J Easler; David M Agarwal; Mackenzie Eagleson; Nicholas J Zyromski; Michael G House; Susannah Ellsworth; Ihab El Hajj; Bert H O'Neil; Attila Nakeeb; Stuart Sherman Journal: Am J Gastroenterol Date: 2017-01-31 Impact factor: 10.864