Neuro-mesenchymal interaction mediated by a β2 adrenergic-nerve growth factor feedforward loop promotes colorectal cancer progression.

Autor:	Kobayashi H; Columbia University Medical Center, New York, NY, United States., Iida T; Nagoya University Graduate School of Medicine, Nagoya, Japan., Ochiai Y; Columbia University Medical Center, New York, NY, United States., Malagola E; Columbia University Medical Center, New York, NY, United States., Zhi X; Columbia University Medical Center, New York, NY, United States., White RA; NYU Langone's Laura and Isaac Perlmutter Cancer Center, New York, NY, United States., Qian J; Columbia University Medical Center, New York, NY, United States., Wu F; Columbia University Medical Center, New York, NY, United States., Waterbury QT; Columbia University Medical Center, New York, NY, United States., Tu R; Union Hospital, Fuzhou, Fujian, China., Zheng B; Columbia University Medical Center, New York, NY, United States., LaBella JS; Columbia University Medical Center, New York, NY, United States., Zamechek LB; Columbia University, New York, New York, United States., Ogura A; Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan., Woods SL; University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia., Worthley DL; Colonoscopy Clinic, Brisbane, QLD, Australia., Enomoto A; Nagoya University, Nagoya, Japan., Wang TC; Columbia University Medical Center, New York, NY, United States.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2024 Aug 13. Date of Electronic Publication: 2024 Aug 13.
DOI:	10.1158/2159-8290.CD-24-0287
Abstrakt:	Cancer-associated fibroblasts (CAFs) and nerves, components of the tumor microenvironment, have each been shown to directly promote gastrointestinal cancers. However, it remains unknown whether these cells interact with each other to regulate cancer progression. We found that in colorectal cancer (CRC) norepinephrine induces ADRB2-dependent nerve growth factor (NGF) secretion from CAFs, which in turn increases intra-tumor sympathetic innervation and norepinephrine accumulation. Adrenergic stimulation accelerates CRC growth through ADRA2A/Gi-mediated activation of Yes-Associated Protein (YAP). NGF from CAFs directly enhances CRC cell growth via the PI3K/AKT pathway. Treatment with a tropomyosin receptor kinase (Trk) inhibitor decreased YAP and AKT activation and CRC progression in mice. In human CRC, high NGF expression is associated with the mesenchymal-like tumor subtype and poor patient survival. These findings suggest a central role for reciprocal CAF-nerve crosstalk in promoting CRC progression. Blocking this feedforward loop with a Trk inhibitor may represent a potential therapeutic approach for CRC.
Databáze:	MEDLINE
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