Related Experiment Video
Updated: Jun 22, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
Tazarotene-induced Gene 1 Induces Melanoma Cell Death by Triggering Endoplasmic Reticulum Stress Response
Chun-Hua Wang1,2, I-Shiang Tzeng3,4, Lu-Kai Wang5
1Department of Dermatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 231 New Taipei City, Taiwan.
Background:
This study investigated the mechanism by which tazarotene-induced gene 1 (TIG1) inhibits melanoma cell growth. The main focus was to analyze downstream genes regulated by TIG1 in melanoma cells and its impact on cell growth.
Methods:
The effects of TIG1 expression on cell viability and death were assessed using water-soluble tetrazolium 1 (WST-1) mitochondrial staining and lactate dehydrogenase release assays. RNA sequencing and Western blot analysis were employed to investigate the genes regulated by TIG1 in melanoma cells. Additionally, the correlation between TIG1 expression and its downstream genes was analyzed in a melanoma tissue array.
Results:
TIG1 expression in melanoma cells was associated with decreased cell viability and increased cell death. RNA-sequencing (RNA-seq), quantitative reverse transcription PCR (reverse RT-QPCR), and immunoblots revealed that TIG1 expression induced the expression of Endoplasmic Reticulum (ER) stress response-related genes such as Homocysteine-responsive endoplasmic reticulum-resident ubiquitin-like domain member 1 (HERPUD1), Binding immunoglobulin protein (BIP), and DNA damage-inducible transcript 3 (DDIT3). Furthermore, analysis of the melanoma tissue array revealed a positive correlation between TIG1 expression and the expression of HERPUD1, BIP, and DDIT3. Additionally, attenuation of the ER stress response in melanoma cells weakened the impact of TIG1 on cell growth.
Conclusions:
TIG1 expression effectively hinders the growth of melanoma cells. TIG1 induces the upregulation of ER stress response-related genes, leading to an increase in caspase-3 activity and subsequent cell death. These findings suggest that the ability of retinoic acid to prevent melanoma formation may be associated with the anticancer effect of TIG1.
Insights
Tazarotene-induced gene 1 (TIG1) inhibits melanoma growth by upregulating endoplasmic reticulum stress genes, leading to cancer cell death. This mechanism highlights TIG1's potential as an anticancer agent.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Melanoma cell growth is a significant challenge in cancer research.
- Understanding the molecular mechanisms of melanoma inhibition is crucial for developing effective treatments.
- Tazarotene-induced gene 1 (TIG1) has been identified as a potential inhibitor of melanoma progression.
Purpose of the Study:
- To elucidate the mechanism by which TIG1 inhibits melanoma cell growth.
- To identify downstream genes regulated by TIG1 in melanoma.
- To assess the impact of TIG1 on melanoma cell viability and death.
Main Methods:
- Assessed cell viability and death using WST-1 and LDH assays.
- Utilized RNA sequencing and Western blot analysis to identify TIG1-regulated genes.
- Analyzed the correlation between TIG1 expression and downstream genes in melanoma tissue arrays.
Main Results:
- TIG1 expression decreased melanoma cell viability and increased cell death.
- TIG1 upregulated endoplasmic reticulum (ER) stress response genes, including HERPUD1, BIP, and DDIT3.
- A positive correlation was observed between TIG1 and ER stress gene expression in melanoma tissues.
- Inhibition of ER stress attenuated the anti-melanoma effect of TIG1.
Conclusions:
- TIG1 effectively inhibits melanoma cell growth.
- TIG1 induces melanoma cell death via upregulation of ER stress response genes and caspase-3 activity.
- The anticancer effects of TIG1 may contribute to retinoic acid's role in preventing melanoma.
Related Concept Videos
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway
The Intrinsic Apoptotic Pathway
Electron Transport Chain: Complex I and II
ROS generation is regulated and maintained at moderate levels necessary...
Regulation of the Unfolded Protein Response
MAPK Signaling Cascades

