2. Academic Validation
  3. Lysophosphatidic acid mediated PI3K/Akt activation contributed to esophageal squamous cell cancer progression

Lysophosphatidic acid mediated PI3K/Akt activation contributed to esophageal squamous cell cancer progression

  • Carcinogenesis. 2021 Apr 30;42(4):611-620. doi: 10.1093/carcin/bgaa143.
Si Liu 1,  Haiyan Jiang 1 2,  Li Min 1,  Tingting Ning 1,  Junxuan Xu 1,  Tiange Wang 1,  Xingyu Wang 1,  Qian Zhang 1,  Ruizhen Cao 3,  Shutian Zhang 1,  Shengtao Zhu 1
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, PR China.
  • 2 Department of Gastroenterology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing 100029, PR China.
  • 3 Department of Gastroenterology, Ordos Central Hospital, National Clinical Research Center for Digestive Disease-Ordos Subcenter, Ordos 017000, Innermongolia, PR China.
PMID: 33367557 DOI: 10.1093/carcin/bgaa143
Abstract

Lysophosphatidic acid (LPA) and its G-protein-coupled receptors (Lpar1-Lpar6) mediate a plethora of activities associated with Cancer growth and progression. However, there is no systematic study about whether and how LPA promotes esophageal squamous cell carcinoma (ESCC). Here, we show that Autotaxin (ATX), a primary LPA-producing Enzyme, is highly expressed in ESCC, and overexpressed ATX is associated with the poor outcome of ESCC patients. Meanwhile, the expression of LPAR1 was much higher in ESCC cells compared with Het-1a (human esophagus normal epithelial cells). Functional experiments showed that LPA remarkably increased the proliferation and migration of ESCC cells. Furthermore, LPAR1 knockdown abolished the effect of LPA on ESCC cell proliferation and migration. Mechanistic studies revealed that LPA promoted ESCC cell lines proliferation and migration through PI3K/Akt pathway. Treatment of KYSE30 cell xenografts with LPAR1 Inhibitor BMS-986020 significantly repressed tumor growth. Our results shed light on the important role of LPA in ESCC, and LPAR1 might be a potential treatment target for ESCC.

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