Related Experiment Video

Updated: Apr 4, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
09:38

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

9.3K

IGFBP2 modulates the chemoresistant phenotype in esophageal adenocarcinoma

Amy L Myers1, Lin Lin1, Derek J Nancarrow1

  • 1Department of Surgery, University of Michigan, Ann Arbor, MI, USA.

Oncotarget
|August 29, 2015
PubMed

Insights

High IGFBP2 expression correlates with treatment resistance in esophageal adenocarcinoma (EAC). Targeting IGFBP2 and related pathways may sensitize resistant EAC tumors to chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Esophageal adenocarcinoma (EAC) often presents at advanced stages with poor therapeutic response rates (<40%).
  • Understanding molecular resistance mechanisms is critical for improving EAC patient outcomes.
  • Insulin-like growth factor-binding protein 2 (IGFBP2) influences cell signaling, growth, invasion, and resistance in various cancers.

Purpose of the Study:

  • To investigate the role of IGFBP2 in esophageal adenocarcinoma (EAC) resistance to therapy.
  • To explore IGFBP2's impact on EAC cell proliferation, migration, and invasion.
  • To determine if targeting IGFBP2 can sensitize EAC cells to chemotherapy.

Main Methods:

  • Assessed IGFBP2 expression in primary EAC tissues and correlated it with clinical outcomes.
  • Modulated IGFBP2 expression in EAC cell lines to study its effects on cellular behavior.
  • Investigated the effects of IGFBP2 knockdown on chemosensitivity to cisplatin in vitro.
  • Examined the involvement of AKT and ERK signaling pathways in IGFBP2-mediated chemosensitization.
  • Tested the efficacy of combining IGFBP2 inhibition with MAPK or PI3K/AKT pathway inhibitors.

Main Results:

  • High IGFBP2 expression was found in a subset of EACs and associated with shorter disease-free intervals and treatment resistance.
  • Increased IGFBP2 expression promoted EAC cell proliferation, migration, and invasion.
  • IGFBP2 knockdown sensitized EAC cells to cisplatin, particularly in a serum-dependent manner.
  • Silencing IGFBP2 altered AKT and ERK pathway activation in response to IGF1 and cisplatin.
  • Inhibitors of MEK1/2 (MAPK pathway) or AKT enhanced cisplatin sensitization in IGFBP2-silenced EAC cells.

Conclusions:

  • IGFBP2 plays a significant role in EAC progression and chemoresistance.
  • Targeting IGFBP2, alone or in combination with MAPK or PI3K/AKT pathway inhibitors, may offer a strategy to overcome neoadjuvant chemotherapy resistance in EAC.
Keywords:
AKTERKIGFBP2chemotherapy resistanceesophageal cancer

More Related Videos

Studying TGF-&#946; Signaling and TGF-&#946;-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

14.8K
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

8.5K

Related Concept Videos

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
68
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...
8.4K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K
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.
2.8K