Related Experiment Video

Updated: Jul 1, 2026

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

NRF1 Activates the AMPK/SIRT1/PGC-1α/TFAM Axis to Suppress EMT and Tumor Progression in Lung Adenocarcinoma

Hsing-Hsien Wu1, Pei-Fang Hsieh2,3, Ming-DER Shi4

  • 1Department of Thoracic Surgery, Tainan Municipal Hospital, Tainan, Taiwan, R.O.C.

Cancer Genomics & Proteomics
|June 29, 2026
PubMed
Abstract

Insights

Nuclear respiratory factor 1 (NRF1) suppresses lung cancer progression by inhibiting epithelial-mesenchymal transition (EMT) and promoting apoptosis. NRF1 is a potential therapeutic target for overcoming treatment resistance in lung cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Lung cancer is a leading cause of cancer mortality worldwide.
  • Identifying molecular drivers of lung cancer progression and therapeutic resistance is crucial.
  • Nuclear respiratory factor 1 (NRF1) influences key cancer processes like mitochondrial biogenesis, apoptosis, and epithelial-mesenchymal transition (EMT).

Purpose of the Study:

  • To investigate the role of Nuclear respiratory factor 1 (NRF1) in lung cancer progression.
  • To evaluate NRF1 as a potential therapeutic target for lung cancer.

Main Methods:

  • Utilized A549 lung adenocarcinoma cells with NRF1 overexpression and silencing.
  • Assessed epithelial-mesenchymal transition (EMT) markers, mitochondrial biogenesis factors, and apoptotic markers via western blotting.
  • Performed functional assays for cell migration and apoptosis, with in vivo validation in SCID mice.

Main Results:

  • NRF1 overexpression inhibited EMT, suppressed cell migration, and enhanced mitochondrial biogenesis and apoptosis.
  • NRF1 silencing promoted EMT, reduced mitochondrial biogenesis, and decreased apoptosis.
  • In vivo studies confirmed NRF1's role in suppressing EMT and enhancing mitochondrial and apoptotic pathways.

Conclusions:

  • Nuclear respiratory factor 1 (NRF1) functions as a suppressor of EMT and a promoter of mitochondrial biogenesis and apoptosis in lung cancer.
  • NRF1's regulatory functions position it as a promising therapeutic target for inhibiting lung cancer progression.
  • Targeting NRF1 may help overcome resistance to conventional lung cancer therapies.
Keywords:
Lung cancerNRF1RNA interferenceapoptosiscell apoptosisepithelial–mesenchymal transitionmitochondrial biogenesismitochondrial dysfunctiontherapeutic targettumor progression

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...