Events The 1st International Online Conference on Diseases

Event submissions

Published

This submission belongs to the session S7. Endocrine and Metabolic Disorders of the event The 1st International Online Conference on Diseases

Published date

04 Sep, 2025

Academic Editor

Andrea Cabrera-Pastor

Citation

Yina Wang, Tumor Cell-Intrinsic NIK Shapes Metabolic Crosstalk Between Tumors and Brown Adipose Tissue, in Proceedings of The 1st International Online Conference on Diseases, 9 September–11 September 2025, MDPI: Basel, Switzerland

Facebook

Twitter

Tumor Cell-Intrinsic NIK Shapes Metabolic Crosstalk Between Tumors and Brown Adipose Tissue

Yina Wang ¹

1. Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA, USA

Abstract

Introduction and Objective: Cancer cachexia pivotally influences morbidity and mortality. Brown adipose tissue (BAT) is aberrantly activated by tumor-derived factors, contributing to weight loss and cachexia. NF-κB-inducing kinase (NIK) is highly activated in cancer cells, prompting us to decipher the role of NIK in tumor-stimulation of BAT.

Methods: NIK was overexpressed (NIK-Tg) or deleted (NIK-KO) specifically in bile duct epithelial cells. NIK-Tg, NIK-KO, and wild-type (WT) control mice were treated with thioacetamine (TAA) to induce intrahepatic cholangiocarcinoma (iCCA). NIK was deleted via CRISPR/Cas9 in HuCCT1 cells (HuCCT1-KO), a human iCCA line. Conditioned medium was prepared from huCCT1-KO and HuCCT1 cells and used to stimulate brown adipocyte culture. HuCCT1-KO and TuCCT1 cells were injected subcutaneously into immunodeficient mice, and tumor growth and BAT activation were assessed.
Results: TAA promoted iCCA to a dramatically higher degree in NIK-Tg than in WT mice; conversely, NIK-KO mice were resistant to TAA-induced iCCA. Likewise, ablation of NIK also markedly suppressed tumor growth from HuCCT1-KO cells relative to tumors from HuCCT1 cells. BAT expression of UCP1 and other thermogenic genes was tremendously higher in tumor-bearing NIK-Tg mice relative to iCCA-free WT mice. Consistently, BAT was activated to a markedly higher level in mice transplanted with HuCCT1 cells (large tumors) relative to mice transplanted with HuCCT1-KO cells (small tumors). HuCCT1-KO conditioned medium activated the thermogenic program in brown adipocyte culture to a substantially higher level than HuCCT1 conditioned medium.
Conclusion: Aberrant activation of biliary NIK increases liver cancer risk. NIK is required for production and secretion of soluble tumor mediators that stimulate BAT and cancer cachexia. NIK inhibitors may serve as a potential medication for the treatment of cancer and cancer cachexia.

Keywords

Cancer

NIK

Adipose tissue

Crosstalk

The association between sleep quality and chronotype in health science students in Morocco and Spain

Fostering reflective learning in Masters students through CDC clinical case studies in clinical parasitology