Testin is a tumor suppressor in non-small cell lung cancer

Wang, Ming; Wang, Qian; Peng, Wenjia; Hu, Jian; Wang, Zuyi; Líu, Hao; Huang, Lingxia

doi:10.3892/or.2016.5316

Cited by 12 publications

(13 citation statements)

References 42 publications

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“…Consistent with our findings, a previous study showed that overexpression of TES significantly inhibited breast cancer cell invasion and reduced breast cancer cell metastasis to the lung through blocking the secretion of matrix metallopeptidase-2 (MMP-2) [18]. Overexpression of TES also markedly inhibited the invasion and metastasis of endometrial carcinoma [19] and non-small cell lung cancer [21]. Thus, TES down-regulation may play important roles in the progression of different types of human cancers.…”

Section: Discussionsupporting

confidence: 90%

“…TES has been identified as a TSG in many types of tumors, such as uterine cancer [7], ovarian carcinoma [17], breast cancer [18], endometrial carcinoma [19], head and neck squamous cell carcinoma [20], and non-small cell lung cancer [21]. In the present study, we investigated the effect of TES on the viability of GC cells both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Chen

Zhao

et al. 2019

Cancer Communications

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BackgroundIn 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.MethodsWe 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.ResultsTES 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.ConclusionsWe believe that TES functions as a Mena-dependent tumor suppressor. TES represents a valuable prognostic marker and potential target for GC treatment.Electronic supplementary materialThe online version of this article (10.1186/s40880-019-0347-y) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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

Wang

Chen

Zhao

et al. 2019

Cancer Communications

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“…Additionally, they presented inhibitory effect of TES on NSCLC cell xenograft formation and growth in vivo on athymic nude mice. These data suggest important role of testin in development and progression of NSCLC [48].…”

Section: Introductionmentioning

confidence: 99%

“…Testin participate in the processes of tumor growth, angiogenesis, and metastasis [10]. Many researchers stated involvement of testin in tumor progression, what suggest its potential usage in immunotherapy [7, 11]. Understanding the molecular functions of testin may be crucial in development personalized treatment.…”

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confidence: 99%

The Role of Testin in Human Cancers

Popiel

Kobierzycki

Dzięgiel

2018

Pathol. Oncol. Res.

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Testin is a protein expressed in almost all normal human tissues. It locates in the cytoplasm along stress fibers being recruited to focal adhesions. Together with zyxin and vasodilator stimulated protein it forms complexes with various cytoskeleton proteins such as actin, talin and paxilin. They jointly play significant role in cell motility and adhesion. In addition, their involvement in the cell cycle has been demonstrated. Expression of testin protein level correlates positively with percentage of cells in G1 phase, while overexpression can induce apoptosis and decreased colony forming ability. Decreased testin expression associate with loss by cells epithelial morphology and gain migratory and invasive properties of mesenchymal cells. Latest reports indicate that TES is a tumor suppressor gene which can contribute to cancerogenesis but the mechanism of loss TES gene expression is still unknown. Some authors point out hypermethylation of the CpG island as a main factor, however loss of heterozygosity may also play an important role [4, 5]. The altered expression of testin was found in malignant neoplasm, i.a. ovarian, lung, head and neck squamous cell cancer, breast, endometrial, colorectal, prostate and gastric cancers [1–9]. Testin participate in the processes of tumor growth, angiogenesis, and metastasis [10]. Many researchers stated involvement of testin in tumor progression, what suggest its potential usage in immunotherapy [7, 11]. Understanding the molecular functions of testin may be crucial in development personalized treatment. In the present manuscript up-to-date review of literature can be found.

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“…In humans, the TES gene is located in the FRG7G region on chromosome 7q31.2, which is believed to contain a tumour suppressor gene because of its lack of heterozygosity in multiple malignancies . The interest in TES mainly arises from the fact that it has been shown to be downregulated in an increasing number of human tumour types, in which its downregulation correlates with disease progression …”

Section: Introductionmentioning

confidence: 99%

Testin protects against cardiac hypertrophy by targeting a calcineurin‐dependent signalling pathway

Liu

Guo

Xiao

et al. 2018

J Cellular Molecular Medi

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Multiple organs express testin (TES), including the heart. Nevertheless, current understanding of the influence of TES on cardiovascular diseases, especially on cardiac hypertrophy and its etiology, is insufficient. This study investigated the influence of TES on cardiac hypertrophy and its etiology. Murine models with excessive TES expression specific to the heart were constructed with an adeno‐associated virus expression system. Cardiac hypertrophy was stimulated through aortic banding (AB). The severity of cardiac hypertrophy was evaluated through molecular, echocardiographic, pathological, and hemodynamic examination. The findings of our study revealed that TES expression was remarkably suppressed not only in failing human hearts but also in mouse hearts with cardiac hypertrophy. It was discovered that excessive TES expression driven by an adeno‐associated viral vector noticeably inhibited hypertrophy triggered by angiotensin II (Ang II) in cultivated cardiomyocytes from newborn rats. It was also revealed that TES knockdown via AdshTES caused the reverse phenotype in cardiomyocytes. Furthermore, it was proved that excessive TES expression attenuated the ventricular dilation, cardiac hypertrophy, dysfunction, and fibrosis triggered by AB in mice. It was discovered that TES directly interacted with calcineurin and suppressed its downstream signalling pathway. Moreover, the inactivation of calcineurin with cyclosporin A greatly offset the exacerbated hypertrophic response triggered by AB in TES knockdown mice. Overall, the findings of our study suggest that TES serves as a crucial regulator of the hypertrophic reaction by hindering the calcineurin‐dependent pathway in the heart.

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Testin is a tumor suppressor in non-small cell lung cancer

Cited by 12 publications

References 42 publications

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

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

The Role of Testin in Human Cancers

Testin protects against cardiac hypertrophy by targeting a calcineurin‐dependent signalling pathway

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