Role of metabolic reprogramming toward fatty acid oxidation on tumor lymph node metastasis

Choong-kun Lee; Seung-hwan Jeong; Cholsoon Jang; Hosung Bae; Yoo Hyung Kim; Intae Park; Sang Kyum Kim; Gou Young Koh

doi:10.1200/JCO.2019.37.15_suppl.e14501

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Role of metabolic reprogramming toward fatty acid oxidation on tumor lymph node metastasis

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Role of metabolic reprogramming toward fatty acid oxidation on tumor lymph node metastasis

Choong-kun Lee, Seung-hwan Jeong, Cholsoon Jang, Hosung Bae, Yoo Hyung Kim, Intae Park, Sang Kyum Kim and Gou Young Koh

Journal of clinical oncology, Vol.37(15_suppl), pp.e14501-e14501

05/20/2019

DOI: 10.1200/JCO.2019.37.15_suppl.e14501

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Abstract

Abstract only e14501 Background: Metastasis of tumors to lymph node (LN) is a strong predictor of cancer patient mortality and determinant of disease progression and treatment options. Despite the clinical significance of tumor LN metastasis, the mechanisms underlying this process remain largely unexplored. Methods: We used comparative transcriptomics and metabolomics analyses of the primary tumor and LN micro- and macro-metastatic tumors from B16F10 murine melanoma model. B16F10 melanoma footpad implantation model and MMTV-PyMT spontaneous breast cancer genetic mouse models were analyzed in vivo. We also investigated the LN-metastatic tumors from sentinel LNs in 21 patients with melanoma. Results: We found that tumor cells undergo dramatic metabolic reprogramming towards fatty acid oxidation (FAO) for successful LN metastasis. Mechanistically, transcription co-activator YAP is selectively activated in LN metastatic tumors, leading to stimulation of FAO gene programs. Pharmacological inhibition of FAO or genetic ablation of YAP in tumors markedly suppressed LN metastasis. Unexpectedly, metastatic tumors highly stimulated the bile acid synthesis pathway upon arrival at the LN, and these bile acids activated YAP of tumor cells via nuclear vitamin D receptor. Lastly, YAP activation in the metastatic LNs of melanoma patients was reversely correlated with distant metastasis–free survival. Conclusions: This study propose that inhibition of FAO or YAP signaling to prevent the metabolic reprogramming of metastatic tumors offers a potential therapeutic strategy for mitigating tumor LN metastasis.

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Title: Subtitle: Role of metabolic reprogramming toward fatty acid oxidation on tumor lymph node metastasis
Creators: Choong-kun Lee - Yonsei University
Seung-hwan Jeong - KAIST, Daejon, South Korea
Cholsoon Jang - Princeton University
Hosung Bae - Korea Advanced Institute of Science and Technology
Yoo Hyung Kim - Korea Advanced Institute of Science and Technology
Intae Park - Institute for Basic Science
Sang Kyum Kim - Yonsei University
Gou Young Koh - Institute for Basic Science
Resource Type: Abstract
Publication Details: Journal of clinical oncology, Vol.37(15_suppl), pp.e14501-e14501
DOI: 10.1200/JCO.2019.37.15_suppl.e14501
ISSN: 0732-183X
eISSN: 1527-7755
Publisher: AMER SOC CLINICAL ONCOLOGY
Language: English
Date published: 05/20/2019
Academic Unit: Internal Medicine
Record Identifier: 9985217013502771

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