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TSPAN1 inhibits metastasis of nasopharyngeal carcinoma via suppressing NF-kB signaling

Cancer Gene Therapy volume 31, pages 454–463 (2024)Cite this article

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Abstract

Nasopharyngeal carcinoma (NPC) originates in the epithelial cells of the nasopharynx and is a common malignant tumor in southern China and Southeast Asia. Metastasis of NPC remains the main cause of death for NPC patients even though the tumor is sensitive to radiotherapy and chemotherapy. Here, we found that the transmembrane protein tetraspanin1 (TSPAN1) potently inhibited the in vitro migration and invasion, as well as, the in vivo metastasis of NPC cells via interacting with the IKBB protein. In addition, TSPAN1 was essential in preventing the overactivation of the NF-kB pathway in TSPAN1 overexpressing NPC cells. Furthermore, reduced TSPAN1 expression was associated with NPC metastasis and the poor prognosis of NPC patients. These results uncovered the suppressive role of TSPAN1 against NF-kB signaling in NPC cells for preventing NPC metastasis. Its therapeutic value warrants further investigation.

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Fig. 1: TSPAN1 mRNA levels are downregulated in high-metastasis NPC cells which is correlated with poorer prognosis in several types of malignancies.
Fig. 2: Overexpressing TSPAN1 suppressed cellular motility while silencing TSPAN1 promoted cellular motility in NPC cells.
Fig. 3: TSPAN1 inhibits NPC metastasis in vivo.
Fig. 4: TSPAN1 prevents the activation of NF-kB signaling.
Fig. 5: TSPAN1 suppresses NF-kB signaling via interacting with IKBB.

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Additional data can be obtained from the corresponding author upon request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 82073220, No. 81872384 and No. 81672872 to CQ, and No. 81972785, No. 81773162 and No. 81572901 to BH, No. 81872085 to YC), the Shandong Provincial Natural Science Foundation of China (No. ZR2021QH208 to DM), Basic and Applied Basic Research Project of Guangzhou Basic Research Program (No. 2023A04J2144 to MW).

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Author notes

  1. These authors contributed equally: Ming-Dian Wang, Hui-Ting Li, Li-Xia Peng.

Authors and Affiliations

  1. Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China

    Ming-Dian Wang & Yun Cao

  2. State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China

    Ming-Dian Wang, Hui-Ting Li, Li-Xia Peng, Yan-Hong Lang, Zhi-Jie Liu, De-Huan Xie, Ling-Ling Guo, Liu-Yan Ding, Bi-Jun Huang, Yun Cao & Chao-Nan Qian

  3. Department of Anesthesiology, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China

    Hui-Ting Li

  4. Department of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, P. R. China

    Yan Mei & Li-Sheng Zheng

  5. Medical School, Pingdingshan University, Pingdingshan, Henan Province, 467021, P. R. China

    Chang-Zhi Li

  6. Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, P. R. China

    Dong-Fang Meng

  7. Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510655, P. R. China

    Liang Xu

  8. Department of radiation oncology, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, P. R. China

    Xing-Si Peng

  9. Department of Radiotherapy, Affiliated Dongguan Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong, China

    Zhi-Jie Liu

  10. Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, P.R. China

    Mao-Guang Ma

  11. Guangzhou Concord Cancer Center, Guangzhou, 510060, P. R. China

    Chao-Nan Qian

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Contributions

MW, YC and CQ designed the project and wrote the paper. MW, HL and LP performed all the experiments. YM and LZ analyzed the GEPIA data. MM, LG and DX performed the in vivo experiments and data analysis. CL, ZL and LD provided advice on discussions. DM, YL, LX and XP supplied RNA from human cancer specimens and collected clinical follow-up data. BH contributed with discussions and advice.

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Correspondence to Yun Cao or Chao-Nan Qian.

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Wang, MD., Li, HT., Peng, LX. et al. TSPAN1 inhibits metastasis of nasopharyngeal carcinoma via suppressing NF-kB signaling. Cancer Gene Ther 31, 454–463 (2024). https://doi.org/10.1038/s41417-023-00716-w

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