The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth

Lin, Yan; Lin, Fengkang; Zhang, Zhuoran; Peng, Lijia; Yang, Wenli; Yang, Mao; Luo, Bo; Wu, Ting; Li, Dabing; Li, Xuesen; Ran, Bing; Anuchapreeda, Songyot; Chaiwongsa, Rujirek; Khamphikham, Pinyaphat; Duangmano, Suwit; Xu, Jianming; He, Tao; Pornprasert, Sakorn

doi:10.7150/ijbs.74574

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Int J Biol Sci 2023; 19(3):744-759. doi:10.7150/ijbs.74574 This issue Cite

Research Paper

The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth

Yan Lin^1,2, Fengkang Lin^1,3, Zhuoran Zhang¹, Lijia Peng¹, Wenli Yang¹, Mao Yang¹, Bo Luo¹, Ting Wu¹, Dabing Li¹, Xuesen Li¹, Bing Ran⁴, Songyot Anuchapreeda², Rujirek Chaiwongsa², Pinyaphat Khamphikham², Suwit Duangmano², Jianming Xu⁵, Tao He^1,✉, Sakorn Pornprasert^2,✉

1. Institute for Cancer Medicine and School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, 646000, China.
2. Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200, Thailand.
3. Department of Physiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou Sichuan, 646000, China.
4. Functional laboratory, School of Basic Medical Sciences, Southwest Medical University, Luzhou Sichuan, 646000, China.
5. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

Citation:

Lin Y, Lin F, Zhang Z, Peng L, Yang W, Yang M, Luo B, Wu T, Li D, Li X, Ran B, Anuchapreeda S, Chaiwongsa R, Khamphikham P, Duangmano S, Xu J, He T, Pornprasert S. The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth. Int J Biol Sci 2023; 19(3):744-759. doi:10.7150/ijbs.74574. https://www.ijbs.com/v19p0744.htm

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Abstract

FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. Inhibition of MEK or ERK1/2 activities, or knockout of ERK2 but not ERK1 suppressed the FGFR1 signaling-promoted FOXQ1 gene expression. Inhibition of ERK2 in ERK1 knockout cells blocked, while ectopic expression of FOXQ1 in ERK2 knockout cells rescued the FGFR1-signaling-promoted cell growth. Mechanistically, c-FOS, an early response transcription factor upregulated by the FGFR1-MEK-ERK2 pathway, bound to the FOXQ1 promoter to mediate the FGFR1 signaling-promoted FOXQ1 expression. These results indicate that the FGFR1-ERK2-c-FOS-FOXQ1 regulatory axis plays an essential role in the FGFR1 signaling-promoted BC growth. Targeting ERK2 and FOXQ1 should block BC growth caused by a deregulated FGFR1 signaling.

Keywords: gene regulation, breast cancer, FGFR1, ERK2, c-FOS, FOXQ1

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APA

Lin, Y., Lin, F., Zhang, Z., Peng, L., Yang, W., Yang, M., Luo, B., Wu, T., Li, D., Li, X., Ran, B., Anuchapreeda, S., Chaiwongsa, R., Khamphikham, P., Duangmano, S., Xu, J., He, T., Pornprasert, S. (2023). The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth. International Journal of Biological Sciences, 19(3), 744-759. https://doi.org/10.7150/ijbs.74574.

ACS

Lin, Y.; Lin, F.; Zhang, Z.; Peng, L.; Yang, W.; Yang, M.; Luo, B.; Wu, T.; Li, D.; Li, X.; Ran, B.; Anuchapreeda, S.; Chaiwongsa, R.; Khamphikham, P.; Duangmano, S.; Xu, J.; He, T.; Pornprasert, S. The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth. Int. J. Biol. Sci. 2023, 19 (3), 744-759. DOI: 10.7150/ijbs.74574.

NLM

CSE

Lin Y, Lin F, Zhang Z, Peng L, Yang W, Yang M, Luo B, Wu T, Li D, Li X, Ran B, Anuchapreeda S, Chaiwongsa R, Khamphikham P, Duangmano S, Xu J, He T, Pornprasert S. 2023. The FGFR1 Signaling Pathway Upregulates the Oncogenic Transcription Factor FOXQ1 to Promote Breast Cancer Cell Growth. Int J Biol Sci. 19(3):744-759.

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