2. Academic Validation
  3. Prenylated PALM2 Promotes the Migration of Esophageal Squamous Cell Carcinoma Cells through Activating Ezrin

Prenylated PALM2 Promotes the Migration of Esophageal Squamous Cell Carcinoma Cells through Activating Ezrin

  • Mol Cell Proteomics. 2023 Jun 14;100593. doi: 10.1016/j.mcpro.2023.100593.
Dan-Xia Deng 1,  Cheng-Yu Li 2,  Zhen-Yuan Zheng 2,  Bing Wen 3,  Lian-Di Liao 1,  Xiao-Jun Zhang 4,  En-Min Li 5,  Li-Yan Xu 6
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China.
  • 2 The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China; Guangdong Esophageal Cancer Research Institute, Shantou Sub-center, Cancer Research Cancer, Shantou University Medical College, Shantou 515041, Guangdong, China.
  • 3 The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China.
  • 4 Central Laboratory, Shantou University Medical College, Shantou 515041, China.
  • 5 The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: nmli@stu.edu.cn.
  • 6 Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, Guangdong, China; Guangdong Esophageal Cancer Research Institute, Shantou Sub-center, Cancer Research Cancer, Shantou University Medical College, Shantou 515041, Guangdong, China. Electronic address: lyxu@stu.edu.cn.
PMID: 37328063 DOI: 10.1016/j.mcpro.2023.100593
Abstract

Proteins containing a CAAX motif at the C-terminus undergo prenylation for localization and activity, and include a series of key regulatory proteins, such as Ras superfamily members, heterotrimeric G proteins, nuclear lamina protein, and several protein kinases and phosphatases. However, studies of prenylated proteins in esophageal Cancer are limited. Here, through research on large-scale proteomic data of esophageal Cancer in our laboratory, we found that paralemmin-2 (PALM2), a potential prenylated protein, was up-regulated and associated with poor prognosis of patients. Low throughput verification showed that the expression of PALM2 in esophageal Cancer tissues was higher than that in their paired normal esophageal epithelial tissues, and it was generally expressed in the membrane and cytoplasm of esophageal Cancer cells. PALM2 interacted with the two subunits of Farnesyl Transferase (FTase), FNTA and FNTB. Either addition of an FTase inhibitor or mutation in the CAAX motif of PALM2 (PALM2C408S) impaired its membranous localization reduced the membrane location of PALM2, indicating PALM2 was prenylated by FTase. Overexpression of PALM2 enhanced the migration of esophageal squamous cell carcinoma (ESCC) cells, whereas PALM2C408S lost this ability. Mechanistically, PALM2 interacted with the N-terminal FERM domain of ezrin of the ezrin/radixin/moesin (ERM) family. Mutagenesis indicated that lysine residues K253/K254/K262/K263 in ezrin's FERM domain and C408 in PALM2's CAAX motif were important for PALM2/ezrin interaction and ezrin activation. Knockout of ezrin prevented enhanced Cancer cell migration by PALM2 overexpression. PALM2, depending on its prenylation, increased both ezrin membrane localization and phosphorylation of ezrin at Y146. In summary, prenylated PALM2 enhances the migration of Cancer cells through activating ezrin.

Keywords

Cell migration; Esophageal squamous cell carcinoma; Ezrin; PALM2; Prenylation.

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