Neuro-Mesenchymal Interaction Mediated by a β2-Adrenergic Nerve Growth Factor Feedforward Loop Promotes Colorectal Cancer Progression

Hiroki Kobayashi; Tadashi Iida; Yosuke Ochiai; Ermanno Malagola; Xiaofei Zhi; Ruth A White; Jin Qian; Feijing Wu; Quin T Waterbury; Ruhong Tu; Biyun Zheng; Jonathan S LaBella; Leah B Zamechek; Atsushi Ogura; Susan L Woods; Daniel L Worthley; Atsushi Enomoto; Timothy C Wang

doi:10.1158/2159-8290.CD-24-0287

Neuro-Mesenchymal Interaction Mediated by a β2-Adrenergic Nerve Growth Factor Feedforward Loop Promotes Colorectal Cancer Progression

Cancer Discov. 2025 Jan 13;15(1):202-226. doi: 10.1158/2159-8290.CD-24-0287.

Authors

Hiroki Kobayashi^{1

2}, Tadashi Iida^{3

4}, Yosuke Ochiai^{1

2

5}, Ermanno Malagola^{1

2}, Xiaofei Zhi^{1

2}, Ruth A White⁶, Jin Qian^{1

2}, Feijing Wu^{1

2}, Quin T Waterbury^{1

2}, Ruhong Tu^{1

2}, Biyun Zheng^{1

2}, Jonathan S LaBella^{1

2}, Leah B Zamechek^{1

2}, Atsushi Ogura⁵, Susan L Woods^{7

8}, Daniel L Worthley^{8

9}, Atsushi Enomoto^{3

10}, Timothy C Wang^{1

2

11}

Affiliations

¹ Division of Digestive and Liver Diseases, Department of Medicine, Irving Cancer Research Center Columbia University Medical Center, New York, New York.
² Columbia University Digestive and Liver Disease Research Center, New York, New York.
³ Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁴ Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁵ Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁶ Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, New York.
⁷ Adelaide Medical School, University of Adelaide, Adelaide, Australia.
⁸ South Australian Health and Medical Research Institute (SAHMRI), Adelaide, Australia.
⁹ Colonoscopy Clinic, Lutwyche, Australia.
¹⁰ Division of Molecular Pathology, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹¹ Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York.

PMID: 39137067
PMCID: PMC11729495 (available on 2025-07-13)
DOI: 10.1158/2159-8290.CD-24-0287

Abstract

Our work demonstrates that the bidirectional interplay between sympathetic nerves and NGF-expressing CAFs drives colorectal tumorigenesis. This study also offers novel mechanistic insights into catecholamine action in colorectal cancer. Inhibiting the neuro-mesenchymal interaction by TRK blockade could be a potential strategy for treating colorectal cancer.

MeSH terms

Animals
Cancer-Associated Fibroblasts / metabolism
Cancer-Associated Fibroblasts / pathology
Cell Line, Tumor
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / metabolism
Colorectal Neoplasms* / pathology
Disease Progression
Epithelial-Mesenchymal Transition
Humans
Mice
Nerve Growth Factor* / genetics
Nerve Growth Factor* / metabolism
Receptors, Adrenergic, beta-2* / metabolism

Substances

Nerve Growth Factor
Receptors, Adrenergic, beta-2
NGF protein, human

Abstract

MeSH terms

Substances

Grants and funding