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Cancer Commun (Lond). 2019 Feb 6;39(1):3. doi: 10.1186/s40880-019-0347-y.

TES functions as a Mena-dependent tumor suppressor in gastric cancer carcinogenesis and metastasis.

Wang DD1,2,3, Chen YB1,2,4, Zhao JJ1,2, Zhang XF1,2, Zhu GC1,2, Weng DS1,2, Pan K1,2, Lv L1,2, Pan QZ1,2, Jiang SS1,2, Wang LL5, Xia JC6,7.

Author information

1
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, Guangdong, P.R. China.
2
Department of Biotherapy, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P.R. China.
3
Shandong Medicinal Biotechnology Centre, Back and Neck Pain Hospital, Shandong Academy of Medical Sciences, Jinan, 250062, Shandong, P.R. China.
4
Genetic and Prenatal Diagnosis Center, Department of Gynecology and Obstetrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, P.R. China.
5
Key Laboratory for Applied Microbiology of Shandong Province, Ecology Institute of Shandong Academy of Sciences, Jinan, 250014, Shandong, P.R. China.
6
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, Guangdong, P.R. China. xiajch@mail.sysu.edu.cn.
7
Department of Biotherapy, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P.R. China. xiajch@mail.sysu.edu.cn.

Abstract

BACKGROUND:

In our previous study, we identified a candidate tumor suppressor gene, testin LIM domain protein (TES), in primary gastric cancer (GC). TES contains three LIM domains, which are specific interacting regions for the cell adhesion and cytoskeleton regulatory proteins. Mena is a known cytoskeleton regulator that regulates the assembly of actin filaments and modulates cell adhesion and motility by interacting with Lamellipodin (Lpd). Therefore, we hypothesized that TES plays a role as tumor suppressor in GC through interacting with Mena. This study aimed to investigate the tumor suppressive functions of TES in GC.

METHODS:

We explored the tumor suppressive effect of TES in GC by in vitro cell proliferation assay, colony formation assay, cell cycle analysis, Transwell assays, and in vivo tumorigenicity and metastasis assays. The interaction of TES and Mena was investigated through immunoprecipitation-based mass spectrometry. We also analyzed the expression of TES and Mena in 172 GC specimens using immunohistochemistry and investigated the clinicopathological and prognostic significance of TES and Mena in GC.

RESULTS:

TES suppressed GC cell proliferation and colony formation, induced cell cycle arrest, and inhibited tumorigenicity in vitro. Additionally, it inhibited GC cell migration and invasion in vitro and suppressed metastasis in vivo. TES interacted with Mena, and inhibited the interaction of Mena with Lpd. Transwell assays suggested that TES suppressed migration and invasion of GC cells in a Mena-dependent fashion. In GC patients with high Mena expression, the expression of TES was associated with tumor infiltration (P = 0.005), lymph node metastasis (P = 0.003), TNM stage (P = 0.003), and prognosis (P = 0.010). However, no significant association was observed in GC patients with low Mena expression.

CONCLUSIONS:

We believe that TES functions as a Mena-dependent tumor suppressor. TES represents a valuable prognostic marker and potential target for GC treatment.

KEYWORDS:

Gastric cancer; Lamellipodin; Mena; TES; Tumor suppressor

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