TC2N, a novel oncogene, accelerates tumor progression by suppressing p53 signaling pathway in lung cancer

Hao, Xianglin; Han, Fei; Zhang, Ning; Chen, Hongqiang; Jiang, Xiao; Li, Yin; Liu, Wenbin; Wang, Dandan; Chen, Jianping; Cui, Zhihong; Ao, Lin; Cao, Jia; Liu, Jinyi

doi:10.1038/s41418-018-0202-8

Cited by 47 publications

(57 citation statements)

References 49 publications

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“…In previous studies, we have demonstrated that the expression of TC2N is upregulated in lung tumor tissues compare with the paired adjacent non-cancerous tissues from the same patient 4 . Upregulated TC2N promoted tumor growth and metastasis and is associated with high histological grade, advanced clinical stage, and thus a poor clinical prognosis of lung cancer patients 4 . In our present study, we found that TC2N is also frequently overexpressed in BC tissues, but is under expressed in adjacent normal tissues, which is coordinated with the expression pattern of TC2N in lung cancer.…”

Section: Discussionmentioning

confidence: 92%

“…For years, the role of TC2N in cancer remains completely unexplored. Until recently, we have identified TC2N as a novel oncogene that acts through suppression of the p53 signaling pathway in human lung cancer 4 . Due to the fact that many genes have a dual role in cancer 5,6 , we intend to further explore the precise role of TC2N in cancer development and progression.…”

Section: Introductionmentioning

confidence: 99%

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Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer

et al. 2019

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Although TC2N has proven to be an oncogene in lung cancer, its biological function and molecular mechanisms in other cancer still remains unclear. Here, we investigate in breast cancer that TC2N expression is sharply overexpressed in breast cancer specimens compared with normal breast specimens, and the low TC2N expression was associated with advanced stage, lymphatic metastasis, larger tumors and shorter survival time. Upregulation of TC2N significantly restrains breast cancer cell proliferation in vitro and tumor growth in vivo. Mechanistically, TC2N blocks AKT signaling in a PI3K dependent and independent way through weakening the interaction between ALK and p55γ or inhibiting the binding of EBP1 and AKT. To sum up, these results unmask an ambivalent role of TC2N in cancer, providing a promising inhibitor for PI3K-AKT signaling.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer

et al. 2019

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“…In addition, copines were demonstrated to effectively increase cellular migration in breast cancer through binding with c-Jun activation domain binding protein-1( 9 ). It was also reported that TC2N served as an oncogene and regulated tumor metastasis in lung cancer, while serving as a tumor suppressor in breast cancer ( 6 , 10 , 11 ). Therefore, due to various genes serving a dual role in cancer, the role of TC2N in different types of cancer should also be investigated.…”

Section: Introductionmentioning

confidence: 94%

“…Tac2-N (TC2N), located on human chromosome 14q32.12, belongs to the carboxyl-terminal type tandem C2 protein family, and is a putative C2 domain-containing protein ( 6 ). Although the function of the C2 domain was originally related to calcium-dependent phospholipid binding, a previous study has also indicated that the C2 domain may be involved in cellular signal transduction and protein-protein interactions ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Tac2‑N serves an oncogenic role and promotes drug resistance in human gastric cancer cells

et al. 2020

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Gastric cancer is one of the most common types of malignancy worldwide. Tac2-N (TC2N) has been reported to serve as either an oncogene or tumor suppressor in numerous different types of cancer; however, the role of TC2N in gastric cancer remains poorly understood. The present study aimed to investigate the role of TC2N in gastric cancer and reveal its regulatory mechanism. A Cell Counting Kit-8 assay was used to analyze the cell proliferation rate, while wound healing and Transwell Matrigel assays were performed to determine the cell migratory and invasive abilities, respectively. Cell cycle distribution was determined by flow cytometric analysis, and the expression levels of TC2N, P-glycoprotein (P-gp), cyclin D1, CDK4, cyclin E1, MMP2, MMP9 and N-Myc downstream regulated gene 1 were analyzed using reverse transcription-quantitative PCR or western blotting. Bioinformatics analysis revealed a high expression of TC2N in patients with gastric cancer. The experimental results revealed that TC2N expression levels were significantly unregulated in gastric cancer cell lines. The knockdown of TC2N in AGS cells significantly inhibited the cell proliferation rate and induced cell cycle arrest at the G0/G1 phase, while downregulating cyclin E1, cyclin D1 and CDK4 expression levels. The knockdown of TC2N also inhibited cell migration and invasion. Furthermore, the knockdown of TC2N improved the sensitivity of AGS cells to cisplatin, paclitaxel and 5-fluorouracil, and downregulated the protein expression levels of P-gp. By contrast, TC2N overexpression exerted the opposite effects in AGS cells. In conclusion, the findings of the present study indicated that the genetic knockdown of TC2N may inhibit cell proliferation, migration and invasion, while inducing cell cycle arrest in the G1/S phase and reversing the drug resistance of AGS cells, which may be partly through inhibiting P-gp expression levels. Thus, TC2N may serve as a novel diagnostic marker and therapeutic target for patients with gastric cancer.

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“…Previous studies have reported the essential roles of protein containing the C2 domain in endocytosis, cellular metabolism and cancer [29][30][31]. TC2N expression is also associated with the prognosis and development of human lung cancer and breast cancer [16][17][18]. Former researchers have found that TC2N overexpression in lung cancer leads to enhancing the proliferation ability and inhibiting apoptosis through the repression of p53 function in a transcription-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of TC2N is associated with poor prognosis in gastric cancer

et al. 2020

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Abstract Background Tac2-N (TC2N) is a tandem C2 domain-containing protein, acting as a novel oncogene or suppressor in different kinds of cancers. However, the status of TC2N expression and its significance in gastric cancer (GC) is still unclear. The present study is aimed to elucidate the clinicopathological significance and prognostic value of TC2N level in GC. Methods We used sequencing data from the Cancer Genome Atlas (TCGA) database to analyze TC2N expression in GC by UALCAN database and Gene Expression Profiling Interactive Analysis tools (GEPIA). TC2N expression level in 12 pairs of fresh GC tissues and adjacent nontumorous tissues was detected by quantitative real-time reverse-transcription polymerase chain reaction(RT-PCR)and Western blot(WB) assays. Immunohistochemical (IHC) staining was used to detect TC2N protein expression in Paraffin-embedded tissues in our center. In vitro proliferation, migration and invasion assays were used to evaluate the effect of TC2N on functional capability of gastric cancer cells. LinkedOmics was used to identify gene expressions associated with TC2N. Results The mRNA and protein expression of TC2N in gastric cancer were both significantly higher than normal gastric mucosa. It was also elevated in gastric cancer cells compared with normal gastric epithelium cell. In vitro assays suggested that TC2N facilitated proliferation, migration and invasion of gastric cancer cells. Bioinformatic analysis showed a widespread impact of TC2N on the transcriptome and a strong interaction with tumor associated genes. We also found that TC2N was an independent prognostic factor for long-term survival in GC patients and its high expression was significantly associated with poor overall survival and recurrence-free survival. Conclusions Our results show that high level of TC2N correlates with poor prognosis in patients with gastric cancer and promotes the development of gastric cancer. Thus, TC2N expression can serve as a prognostic biomarker for patients with gastric cancer.

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TC2N, a novel oncogene, accelerates tumor progression by suppressing p53 signaling pathway in lung cancer

Cited by 47 publications

References 49 publications

Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer

Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer

Tac2‑N serves an oncogenic role and promotes drug resistance in human gastric cancer cells

Overexpression of TC2N is associated with poor prognosis in gastric cancer

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