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

被引:6
作者
Deng, Dan-Xia [1 ]
Li, Cheng-Yu [2 ,3 ]
Zheng, Zhen-Yuan [2 ,3 ]
Wen, Bing [2 ]
Liao, Lian-Di [1 ]
Zhang, Xiao-Jun [4 ]
Li, En -Min [2 ]
Xu, Li-Yan [1 ,3 ]
机构
[1] Shantou Univ, Inst Oncol Pathol, Guangdong Prov Key Lab Infect Dis & Mol Immunopath, Med Coll, Shantou, Guangdong, Peoples R China
[2] Shantou Univ, Dept Biochem & Mol Biol, High Canc Incidence Coastal Chaoshan Area, Key Lab Mol Biol,Med Coll, Shantou, Guangdong, Peoples R China
[3] Shantou Univ, Guangdong Esophageal Canc Res Inst, Shantou Sub Ctr, Canc Res Ctr,Med Coll, Shantou, Guangdong, Peoples R China
[4] Shantou Univ, Cent Lab, Med Coll, Shantou, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
PROTEIN PRENYLATION; K-RAS; LAMIN-B; GROWTH; FARNESYLTRANSFERASE; MISLOCALIZATION; ISOPRENYLATION; PROLIFERATION; INVASIVENESS; ASSOCIATION;
D O I
10.1016/j.mcpro.2023.100593
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 upregulated and associated with poor prognosis in 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 the addition of an FTase inhibitor or mutation in the CAAX motif of PALM2 (PALM2C408S) impaired its membranous localization and reduced the membrane location of PALM2, indicating PALM2 was prenylated by FTase. Overexpression of PALM2 enhanced the migration of esophageal squamous cell carcinoma 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 by activating ezrin.
引用
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页数:17
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