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SCI 17 November 2024 Sympathetic Neurons Promote Small Cell Lung Cancer Through the Beta-2 Adrenergic Receptor (Cancer discovery, if=29.7) Fnu T, Shi P, Zhang W, Chung SSW, Damoci CB, Fang Y, Chen QY, Saqi A, Huang Y, Wu X, Lu C, Yang D, Wang TC, Que J. Correspondence: jq2240@cumc.columbia.edu The vagal nerve is linked to tumorigenesis in multiple tissues including small cell lung cancer (SCLC). However, the role of sympathetic neuron in SCLC development remains unknown. Here, we observed a significant reduction in tumor growth following chemical denervation of local sympathetic nerves in a mouse model of SCLC. Further study identified that β2-adrenergic receptor (ADRB2) on cancer cells mediated the crosstalk with nerve fibers. Genetic deletion or pharmacological inhibition of ADRB2 led to reduced tumor growth and improved survival. Moreover, blocking ADRB2 also reduced the growth of human SCLC organoids and xenografts. Further studies revealed that ADRB2 promoted cancer cell expansio
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