Related Experiment Video

Updated: Mar 4, 2026

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
06:24

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line

Published on: April 11, 2025

964

The TRIB1-PPARγ Axis Regulates Cholesterol Metabolism in Pancreatic Ductal Adenocarcinoma

Rui Sun1, Henan Qin1, Wenhe Zhang1

  • 1The First Affiliated Hospital of Dalian Medical University, Dalian, China.

Annals of the New York Academy of Sciences
|March 3, 2026
PubMed

Insights

Tribbles homolog 1 (TRIB1) drives pancreatic cancer by disrupting cholesterol metabolism via the PPARγ-HMGCR pathway. Targeting this axis with statins may improve treatment outcomes for pancreatic ductal adenocarcinoma (PDAC) patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Metabolic Pathways

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) exhibits metabolic reprogramming, including altered cholesterol metabolism.
  • The specific molecular mechanisms driving these metabolic changes in PDAC are not fully understood.

Purpose of the Study:

  • To investigate the role of Tribbles homolog 1 (TRIB1) in PDAC.
  • To elucidate the molecular mechanisms by which TRIB1 influences PDAC progression and cholesterol biosynthesis.
  • To evaluate TRIB1 as a potential biomarker for statin therapy.

Main Methods:

  • Analysis of TRIB1 expression in PDAC tissues.
  • Functional studies involving TRIB1 knockdown and overexpression in PDAC cells.
  • Investigation of the interaction between TRIB1 and PPARγ.
  • Assessment of HMGCR activity and cholesterol biosynthesis.
  • In vivo studies evaluating tumor response to atorvastatin.

Main Results:

  • TRIB1 is upregulated in PDAC and correlates with poor prognosis.
  • TRIB1 knockdown inhibits PDAC cell growth and tumor formation; overexpression promotes them.
  • TRIB1 physically interacts with PPARγ, inhibiting its transcriptional activity.
  • This inhibition leads to derepression of HMGCR, enhancing cholesterol biosynthesis.
  • PDAC tumors with high TRIB1 expression show increased sensitivity to atorvastatin.

Conclusions:

  • The TRIB1-PPARγ-HMGCR axis is crucial for metabolic adaptation in PDAC.
  • TRIB1 promotes PDAC progression by fueling cholesterol biosynthesis.
  • TRIB1 may serve as a predictive biomarker for statin-based therapies in PDAC.
Keywords:
PPARγTRIB1cholesterol synthesismetabolic reprogrammingpancreatic ductal adenocarcinoma

More Related Videos

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma06:21

Ultrasound-Guided Orthotopic Implantation of Murine Pancreatic Ductal Adenocarcinoma

Published on: November 19, 2019

12.3K
Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets07:08

Author Spotlight: Reprogramming Cancer Cells to iPSCs to Study Disease Progression and Treatment Targets

Published on: February 2, 2024

1.5K

Related Concept Videos

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.8K
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
1.7K
Chronic Pancreatitis I: Introduction01:24

Chronic Pancreatitis I: Introduction

The pancreas, an elongated and flat gland situated behind the stomach, serves a vital function in digesting food and managing blood sugar levels.
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
811
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...
5.3K
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...
5.9K
Chronic Pancreatitis II: Collaborative Care01:29

Chronic Pancreatitis II: Collaborative Care

The management of chronic pancreatitis is multifaceted, involving a comprehensive approach that includes thorough assessment, diagnostic testing, and a variety of management strategies.
Assessment:
440