Related Experiment Video

Updated: Jun 13, 2025

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
13:34

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

Published on: April 6, 2016

10.2K

CIB2 mediates acquired gefitinib resistance by inducing ZEB1 expression and epithelial-mesenchymal transition

Feng-Mei Zhou1, Kun-Kun Wang1, Li-Hong Wang1

  • 1Academy of Medical Science, Zhengzhou University, Zhengzhou 450000, China.

Aging
|September 12, 2024
PubMed

Insights

High CIB2 expression drives gefitinib resistance in non-small cell lung cancer (NSCLC) by promoting EMT via ZEB1. Targeting CIB2 may overcome acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib are first-line treatments for advanced non-small cell lung cancer (NSCLC) with EGFR mutations.
  • Acquired resistance to gefitinib remains a significant clinical challenge, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To investigate the role of CIB2 in acquired gefitinib resistance in NSCLC.
  • To elucidate the molecular mechanisms underlying CIB2-mediated gefitinib resistance.

Main Methods:

  • Analysis of CIB2 expression in gefitinib-resistant NSCLC cells.
  • CIB2 knockout and overexpression studies in lung cancer cell lines.
  • Investigation of the effects of CIB2 inhibition on cell apoptosis and epithelial-to-mesenchymal transition (EMT).
  • Assessment of CIB2's role in gefitinib resistance *in vivo*.

Main Results:

  • High CIB2 expression was observed in gefitinib-resistant NSCLC cells.
  • CIB2 knockout increased sensitivity to gefitinib, while CIB2 overexpression induced resistance.
  • CIB2 inhibition significantly promoted apoptosis in resistant cells.
  • Upregulated CIB2 promoted EMT via ZEB1, and FOSL1 transcriptionally regulated CIB2.
  • CIB2 conferred gefitinib resistance in *in vivo* tumor models.

Conclusions:

  • Upregulated CIB2 promotes EMT through ZEB1, contributing to acquired gefitinib resistance in NSCLC.
  • CIB2 represents a potential therapeutic target for overcoming acquired resistance to EGFR-TKIs in NSCLC patients.
Keywords:
CIB2EMTgefitinibnon-small cell lung cancertumor growth

More Related Videos

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

12.8K
Induction and Analysis of Epithelial to Mesenchymal Transition10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

35.7K

Related Concept Videos

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...
6.4K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
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...
4.7K
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
3.0K
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...
13.5K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K