Related Experiment Video

Updated: Jul 29, 2025

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

1.6K

BEX1 mediates sorafenib resistance in hepatocellular carcinoma by regulating AKT signaling

Na Zhuang1, Zhiyun Gu1, Juan Feng1

  • 1Research Center for Precision Medicine, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China.

Cellular Signalling
|May 20, 2023
PubMed

Insights

This study identifies BEX1 as a key factor in hepatocellular carcinoma (HCC) resistance to sorafenib. Lower BEX1 levels predict poor prognosis, suggesting BEX1 as a potential biomarker for HCC treatment.

Area of Science:

  • Hepatocellular Carcinoma Research
  • Cancer Biology
  • Molecular Oncology

Background:

  • Sorafenib is a first-line treatment for advanced hepatocellular carcinoma (HCC).
  • Acquired resistance to sorafenib limits its effectiveness in HCC treatment.
  • Mechanisms underlying sorafenib resistance in HCC are not fully understood.

Purpose of the Study:

  • To identify key mediators of sorafenib resistance in hepatocellular carcinoma.
  • To investigate the role of BEX1 in sorafenib sensitivity and patient prognosis.

Main Methods:

  • Analysis of BEX1 expression in sorafenib-resistant HCC cell lines and xenograft models.
  • Examination of BEX1 expression in The Cancer Genome Atlas (TCGA) database.
  • Kaplan-Meier (K-M) survival analysis.
  • Loss- and gain-of-function studies to assess BEX1's regulatory role.
  • Investigation of BEX1's effect on apoptosis and Akt phosphorylation.

Main Results:

  • BEX1 expression is significantly reduced in sorafenib-resistant HCC cells and models.
  • Down-regulated BEX1 expression is observed in HCC tissues compared to normal liver tissues.
  • Reduced BEX1 expression correlates with poor clinical prognosis in HCC patients.
  • BEX1 regulates sorafenib's cell-killing efficacy by inducing apoptosis and inhibiting Akt phosphorylation.

Conclusions:

  • BEX1 acts as a crucial mediator of sorafenib resistance in hepatocellular carcinoma.
  • BEX1 functions by promoting apoptosis and negatively regulating Akt phosphorylation.
  • BEX1 represents a potential predictive biomarker for assessing prognosis in HCC patients.
Keywords:
AKT signalingBEX1Hepatocellular carcinomaSorafenib resistance

More Related Videos

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis06:38

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

8.9K
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

8.3K

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...
3.7K
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...
3.8K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.7K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K
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...
5.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K