2. Academic Validation
  3. LPCAT1 reprogramming cholesterol metabolism promotes the progression of esophageal squamous cell carcinoma

LPCAT1 reprogramming cholesterol metabolism promotes the progression of esophageal squamous cell carcinoma

  • Cell Death Dis. 2021 Sep 13;12(9):845. doi: 10.1038/s41419-021-04132-6.
Mingyue Tao  # 1 2,  Jing Luo  # 3,  Tong Gu  # 2,  Xiaojuan Yu 2,  Zhen Song 4,  Yali Jun 1,  Hao Gu 1,  Kairong Han 1,  Xiujuan Huang 1,  Weiyong Yu 2,  Su'an Sun 5,  Zhengwei Zhang 5,  Lu Liu 5,  Xiaofei Chen 2,  Li Zhang 6 7,  Chao Luo 8 9,  Qilong Wang 10 11
Affiliations

Affiliations

  • 1 Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, 223300, Huai'an, China.
  • 2 Department of Clinical Oncology, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, 223300, Huaian, P.R. China.
  • 3 Institute of Reproductive Health, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430000, Wuhan, China.
  • 4 Molecular Bioinformatics Group, Faculty of Computer Science and Mathematics, Institute of Computer Science, Frankfurt am Main, Germany.
  • 5 Department of Pathology, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, 223300, Huai'an, China.
  • 6 Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, 223300, Huai'an, China. zhangl@njmu.edu.cn.
  • 7 Biological Sample Bank of Esophageal Cancer, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, 223300, Huai'an, China. zhangl@njmu.edu.cn.
  • 8 Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, 223300, Huai'an, China. hayylch@njmu.edu.cn.
  • 9 Biological Sample Bank of Esophageal Cancer, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, 223300, Huai'an, China. hayylch@njmu.edu.cn.
  • 10 Department of Central Laboratory, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, 223300, Huai'an, China. qlwang@njmu.edu.cn.
  • 11 Biological Sample Bank of Esophageal Cancer, The Affiliated Huaian No.1 People's Hospital, Nanjing Medical University, 223300, Huai'an, China. qlwang@njmu.edu.cn.
  • # Contributed equally.
PMID: 34518524 DOI: 10.1038/s41419-021-04132-6
Abstract

Tumor cells require high levels of Cholesterol for membrane biogenesis for rapid proliferation during development. Beyond the acquired Cholesterol from low-density lipoprotein (LDL) taken up from circulation, tumor cells can also biosynthesize Cholesterol. The molecular mechanism underlying Cholesterol anabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are unclear. Dysregulation of lipid metabolism is common in Cancer. Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) has been implicated in various Cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we identified that LPCAT1 is highly expressed in ESCC and that LPCAT1 reprograms Cholesterol metabolism in ESCC. LPCAT1 expression was negatively correlated with patient prognosis. Cholesterol synthesis in ESCC cells was significantly inhibited following LPCAT1 knockdown; cell proliferation, invasion, and migration were significantly reduced, along with the growth of xenograft subcutaneous tumors. LPCAT1 could regulate the expression of the Cholesterol synthesis Enzyme, SQLE, by promoting the activation of PI3K, thereby regulating the entry of SP1/SREBPF2 into the nucleus. LPCAT1 also activates EGFR leading to the downregulation of INSIG-1 expression, facilitating the entry of SREBP-1 into the nucleus to promote Cholesterol synthesis. Taken together, LPCAT1 reprograms tumor cell Cholesterol metabolism in ESCC and can be used as a potential treatment target against ESCC.

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