# Investigating Novel Functions for NIK/MAP3K14 in High-Grade Glioma

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2022 · $324,844

## Abstract

PROJECT SUMMARY
Cancer cells are able to adapt to grow uncontrollably and invasively in environments with limited availability
of nutrients — most notably, glucose and oxygen. Indeed, the aggressive migration and invasion of high-
grade gliomas, including glioblastoma multiforme (GBM), into healthy brain tissue are major factors
contributing to the therapy resistance and poor prognosis of this malignancy. While many cancer cells
preferentially utilize glycolysis to support growth, GBM cells have been shown to rely on both glycolysis and
mitochondrial metabolism for glucose energy utilization. Mitochondrial dynamics, or the balance between
mitochondrial fission and fusion, is a central mechanism for bioenergetic adaptations to cellular stresses
such as nutrient deprvation. Therefore, targeting de-regulated mitochondrial function is a highly attractive
therapeutic strategy for GBM. Recent findings have established key roles for NF-κB-inducing kinase
(NIK/MAP3K14) in regulating mitochondrial dynamics and subcellular trafficking to promote the
invasiveness and pathogenesis of GBM cells. Moreover, preliminary data demonstrate that mitochondrial
NIK enhances the resistance of GBM cells to nutrient/glucose starvation through regulation of mitochondrial
metabolism. Moreover, the mitochondrial actions of NIK are independent of its regulation of NF-κB activity.
However, the molecular mechanisms by which NIK coordinates regulation of mitochondrial function and
metabolic reprogramming in GBM cells are currently not known. This proposal tests the hypothesis that NIK
is induced by, and is an important regulator of, mitochondrial dynamics, cancer cell metabolism and
infiltrative growth in response to nutrient deprivation. The goals of the proposal are to functionally define
NIK-dependent regulatory networks and metabolic pathways that regulate cancer cell mitochondrial
functions and test the whether NIK inhibition will sensitize GBM cells to nutrient starvation and attenuate
tumor cell survival and pathogenesis. This proposal is anticipated to have an important positive impact
because understanding the molecular basis of NIK mitochondrial functions is likely to generate strong
justification for the development of novel, mechanism-based therapies for GBM that target mitochondrial
dysfunction, invasion, and de-regulated metabolism through NIK inhibition with the ultimate goal of
improving patient survival.
!

## Key facts

- **NIH application ID:** 10402385
- **Project number:** 5R01NS082554-08
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** RAQUEL SITCHERAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $324,844
- **Award type:** 5
- **Project period:** 2014-03-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10402385

## Citation

> US National Institutes of Health, RePORTER application 10402385, Investigating Novel Functions for NIK/MAP3K14 in High-Grade Glioma (5R01NS082554-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10402385. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*