1. Academic Validation
  2. Leukemia inhibitory factor drives glucose metabolic reprogramming to promote breast tumorigenesis

Leukemia inhibitory factor drives glucose metabolic reprogramming to promote breast tumorigenesis

  • Cell Death Dis. 2022 Apr 19;13(4):370. doi: 10.1038/s41419-022-04820-x.
Xuetian Yue  # 1 Jianming Wang  # 1 Chun-Yuan Chang 1 Juan Liu 1 Xue Yang 1 Fan Zhou 1 Xia Qiu 1 Vrushank Bhatt 2 Jessie Yanxiang Guo 2 3 4 Xiaoyang Su 3 5 Lanjing Zhang 6 7 Zhaohui Feng 8 9 Wenwei Hu 10 11
Affiliations

Affiliations

  • 1 Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.
  • 2 Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.
  • 3 Department of Medicine, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
  • 4 Department of Chemical Biology, Rutgers Ernest Mario School of Pharmacy, Piscataway, NJ, USA.
  • 5 Metabolomics Shared Resource, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.
  • 6 Department of Pathology, Princeton Medical Center, Plainsboro, NJ, USA.
  • 7 Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
  • 8 Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA. fengzh@cinj.rutgers.edu.
  • 9 Department of Pharmacology, Rutgers University, Piscataway, NJ, USA. fengzh@cinj.rutgers.edu.
  • 10 Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA. wh221@cinj.rutgers.edu.
  • 11 Department of Pharmacology, Rutgers University, Piscataway, NJ, USA. wh221@cinj.rutgers.edu.
  • # Contributed equally.
Abstract

LIF, a multifunctional cytokine, is frequently overexpressed in many types of solid tumors, including breast Cancer, and plays an important role in promoting tumorigenesis. Currently, how LIF promotes tumorigenesis is not well-understood. Metabolic reprogramming is a hallmark of Cancer cells and a key contributor to Cancer progression. However, the role of LIF in Cancer metabolic reprogramming is unclear. In this study, we found that LIF increases glucose uptake and drives glycolysis, contributing to breast tumorigenesis. Blocking glucose uptake largely abolishes the promoting effect of LIF on breast tumorigenesis. Mechanistically, LIF overexpression enhances glucose uptake via activating the Akt/GLUT1 axis to promote glycolysis. Blocking the Akt signaling by shRNA or its inhibitors greatly inhibits glycolysis driven by LIF and largely abolishes the promoting effect of LIF on breast tumorigenesis. These results demonstrate an important role of LIF overexpression in glucose metabolism reprogramming in breast cancers, which contributes to breast tumorigenesis. This study also reveals an important mechanism underlying metabolic reprogramming of breast cancers, and identifies LIF and its downstream signaling as potential therapeutic targets for breast cancers, especially those with LIF overexpression.

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