STMN1 Promotes Tumor Metastasis in Non-small Cell Lung Cancer Through Microtubule-dependent And Nonmicrotubule-dependent Pathways

Zeng, Lizhong; Lyu, Xin; Yuan, Jingyan; Chen, Yang; Wen, Haimei; Zhang, Lei; Shi, Jie; Liu, Boxuan; Li, Wei; Yang, Shuanying

doi:10.7150/ijbs.84738

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Int J Biol Sci 2024; 20(4):1509-1527. doi:10.7150/ijbs.84738 This issue Cite

Research Paper

STMN1 Promotes Tumor Metastasis in Non-small Cell Lung Cancer Through Microtubule-dependent And Nonmicrotubule-dependent Pathways

Lizhong Zeng¹, Xin Lyu¹, Jingyan Yuan¹, Yang Chen¹, Haimei Wen¹, Lei Zhang², Jie Shi¹, Boxuan Liu¹, Wei Li¹, Shuanying Yang^1✉

1. Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng District, Xi'an 710004, Shaanxi, P.R. China.
2. Department of Pharmacy, Shaanxi Provincial Hospital of Chinese Medicine, Xi'an, China, Xi'an 710061, Shaanxi, P.R. China.

Citation:

Zeng L, Lyu X, Yuan J, Chen Y, Wen H, Zhang L, Shi J, Liu B, Li W, Yang S. STMN1 Promotes Tumor Metastasis in Non-small Cell Lung Cancer Through Microtubule-dependent And Nonmicrotubule-dependent Pathways. Int J Biol Sci 2024; 20(4):1509-1527. doi:10.7150/ijbs.84738. https://www.ijbs.com/v20p1509.htm

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Abstract

The relationship between STMN1 and cancer metastasis is controversial. The purpose of this study was to explore the role and mechanism of STMN1 in NSCLC metastasis. In this study, we reported that STMN1 was highly expressed in NSCLC tissues and associated with poor prognosis. Both in vivo and in vitro functional assays confirmed that STMN1 promoted NSCLC metastasis. Further studies confirmed that STMN1 promoted cell migration by regulating microtubule stability. The results of Co-IP and LC‒MS/MS illustrated that STMN1 interacts with HMGA1. HMGA1 decreases microtubule stability by regulating the phosphorylation level of STMN1 at Ser16 and Ser38 after interacting with STMN1. This result suggested that STMN1 could be activated by HMGA1 to further promote NSCLC metastasis. Meanwhile, it has been found that STMN1 could promote cell migration by activating the p38MAPK/STAT1 signaling pathway, which is not dependent on microtubule stability. However, activating p38MAPK can decrease microtubule stability by promoting the dephosphorylation of STMN1 at ser16. A positive feedback loop was formed between STMN1 and p38MAPK to synergistically promote cell migration. In summary, our study demonstrated that STMN1 could promote NSCLC metastasis through microtubule-dependent and nonmicrotubule-dependent mechanisms. STMN1 has the potential to be a therapeutic target to inhibit metastasis.

Keywords: STMN1, HMGA1, p38MAPK/STAT1, Epithelial-mesenchymal transition, Non-small cell lung cancer

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APA

Zeng, L., Lyu, X., Yuan, J., Chen, Y., Wen, H., Zhang, L., Shi, J., Liu, B., Li, W., Yang, S. (2024). STMN1 Promotes Tumor Metastasis in Non-small Cell Lung Cancer Through Microtubule-dependent And Nonmicrotubule-dependent Pathways. International Journal of Biological Sciences, 20(4), 1509-1527. https://doi.org/10.7150/ijbs.84738.

ACS

Zeng, L.; Lyu, X.; Yuan, J.; Chen, Y.; Wen, H.; Zhang, L.; Shi, J.; Liu, B.; Li, W.; Yang, S. STMN1 Promotes Tumor Metastasis in Non-small Cell Lung Cancer Through Microtubule-dependent And Nonmicrotubule-dependent Pathways. Int. J. Biol. Sci. 2024, 20 (4), 1509-1527. DOI: 10.7150/ijbs.84738.

NLM

CSE

Zeng L, Lyu X, Yuan J, Chen Y, Wen H, Zhang L, Shi J, Liu B, Li W, Yang S. 2024. STMN1 Promotes Tumor Metastasis in Non-small Cell Lung Cancer Through Microtubule-dependent And Nonmicrotubule-dependent Pathways. Int J Biol Sci. 20(4):1509-1527.

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