The extracellular SEMA domain attenuates intracellular apoptotic signaling of semaphorin 6A in lung cancer cells

被引：18

作者：

Shen, Cheng-Ying ^{[1
]}

Chang, Ya-Chu ^{[2
]}

Chen, Li-Han ^{[3
]}

Lin, Wen-Chun ^{[4
]}

Lee, Yung-Hua ^{[3
]}

Yeh, Shu-Tsen ^{[2
]}

Chen, Hsin-Kuang ^{[2
]}

Fang, Wentao ^{[5
]}

Hsu, Chung-Ping ^{[6
]}

Lee, Jang-Ming ^{[7
]}

Lu, Tzu-Pin ^{[8
]}

Hsiao, Pei-Wen ^{[9
]}

Lai, Liang-Chuan ^{[4
,10
]}

Tsai, Mong-Hsun ^{[1
,4
,9
,11
,12
]}

Chuang, Eric Y. ^{[3
,4
,8
,11
,12
,13
]}

机构：

[1] Natl Taiwan Univ, Inst Biotechnol, Taipei, Taiwan

[2] Natl Taiwan Univ, YongLin Biomed Engn Ctr, Taipei, Taiwan

[3] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei, Taiwan

[4] Natl Taiwan Univ, Genome & Syst Biol Degree Program, Taipei, Taiwan

[5] Shanghai Cheset Hosp, Dept Thorac Surg, Shanghai, Peoples R China

[6] Taichung Vet Gen Hosp, Div Thorac Surg, Taichung, Taiwan

[7] Natl Taiwan Univ, Dept Surg, Taipei, Taiwan

[8] Natl Taiwan Univ, Inst Epidemiol & Prevent Med, Taipei, Taiwan

[9] Acad Sinica, Agr Biotechnol Res Ctr, Taipei, Taiwan

[10] Natl Taiwan Univ, Grad Inst Physiol, Taipei, Taiwan

[11] Natl Taiwan Univ, Ctr Biotechnol, Taipei, Taiwan

[12] Natl Taiwan Univ, Ctr Genom Med, Bioinformat & Biostat Core, Taipei, Taiwan

[13] China Med Univ, Sch Chinese Med, Taichung, Taiwan

来源：

ONCOGENESIS | 2018年 / 7卷

关键词：

RECEPTOR; PLEXIN-A4; FADD; IDENTIFICATION; EXPRESSION; BIOMARKER; PROTEIN; GROWTH; ROLES; 5A;

D O I：

10.1038/s41389-018-0105-z

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Semaphorin 6A (SEMA6A), a membrane-bound protein, is downregulated in lung cancer tissue compared to its adjacent normal tissue. However, the functions of SEMA6A in lung cancer cells are still unclear. In the present study, full length SEMA6A and various truncations were transfected into lung cancer cells to investigate the role of the different domains of SEMA6A in cell proliferation and survival, apoptosis, and in vivo tumor growth. SEMA6A-induced cell signaling was explored using gene silencing, co-immunoprecipitation, and co-culture assays. Our results showed that overexpression of SEMA6A reduced the growth of lung cancer cells in vitro and in vivo, and silencing SEMA6A increased the proliferation of normal lung fibroblasts. Truncated SEMA6A lacking the SEMA domain or the extracellular region induced more apoptosis than full length SEMA6A, and reintroducing the SEMA domain attenuated the apoptosis. Fas-associated protein with death domain (FADD) bound to the cytosolic region of truncated SEMA6A and was involved in SEMA6A-associated cytosol-induced apoptosis. This study suggests a novel function of SEMA6A in inducing apoptosis via FADD binding in lung cancer cells.

引用

页数：10

共 38 条

[1] Semaphorin 4D provides a link between axon guidance processes and tumor-induced angiogenesis [J].