Related Experiment Video

Updated: Oct 1, 2025

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
09:38

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

Published on: June 26, 2019

8.1K

Integrin subunit beta 8 contributes to lenvatinib resistance in HCC

Wei Hou1,2, Bryan Bridgeman1,2, Greg Malnassy1,2

  • 1Department of Surgery, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.

Hepatology Communications
|March 3, 2022
PubMed

Insights

Integrin subunit beta 8 (ITGB8) drives lenvatinib resistance in liver cancer. Targeting the ITGB8/HSP90/AKT pathway can overcome this resistance, offering a new therapeutic strategy for hepatocellular carcinoma (HCC) patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Resistance Mechanisms

Background:

  • Lenvatinib is a key treatment for advanced hepatocellular carcinoma (HCC).
  • Drug resistance frequently limits lenvatinib efficacy in HCC.
  • Mechanisms underlying lenvatinib resistance remain largely undefined.

Purpose of the Study:

  • To identify novel molecular drivers of lenvatinib resistance in HCC.
  • To elucidate the functional role of identified targets in mediating resistance.
  • To explore potential therapeutic strategies to overcome lenvatinib resistance.

Main Methods:

  • Established two lenvatinib-resistant (LR) HCC cell lines.
  • Assessed the expression and function of integrin subunit beta 8 (ITGB8) in LR and sensitive HCC cells.
  • Investigated the role of ITGB8 in lenvatinib resistance in vitro and in vivo.
  • Explored the downstream signaling pathways involving HSP90 and AKT.
  • Evaluated the efficacy of targeting the ITGB8/HSP90/AKT axis with specific inhibitors.

Main Results:

  • Elevated ITGB8 expression was identified in LR HCC cells.
  • Silencing ITGB8 reversed lenvatinib resistance, while its ectopic expression conferred resistance.
  • ITGB8 mediated resistance via HSP90-dependent stabilization of AKT and enhanced AKT signaling.
  • AKT inhibitor MK-2206 and HSP90 inhibitor 17-AAG resensitized LR HCC cells to lenvatinib.

Conclusions:

  • ITGB8 is a critical mediator of lenvatinib resistance in HCC.
  • The ITGB8/HSP90/AKT signaling axis plays a pivotal role in this resistance.
  • Targeting the ITGB8/HSP90/AKT pathway represents a promising therapeutic approach for lenvatinib-resistant HCC.

More Related Videos

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure09:38

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

8.9K
A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors12:40

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors

Published on: December 7, 2014

15.0K

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.9K
Non-LTR Retrotransposons03:18

Non-LTR Retrotransposons

As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
12.0K
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
3.7K
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.2K
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.
2.3K