ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis

Sep 21, 2026

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Anoikis resistance is a key driver of metastatic progression in multiple malignancies, yet the molecular basis of anoikis resistance in gastric cancer remains insufficiently defined. This study evaluates Integrin beta-like 1 (ITGBL1) in regulating anoikis resistance and metastasis in gastric cancer cells and models. ITGBL1 overexpression increases anoikis resistance and metastatic capacity, whereas ITGBL1 knockdown suppresses both in vitro and in vivo.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages16

Reading Time40 min

AccessFree to download

Introduction

Background on gastric cancer and metastasis

Anoikis and metastatic viability

Mechanisms of anoikis resistance in other cancers

Knowledge gap: mechanisms in gastric cancer

Study focus (ITGBL1 and AKT/FBLN2 axis)

DOI: 10. 1111/jcmm.18113 OR I G I NAL ART I C L E ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis Kanger Shen1,2,3 | Wei Xia3 | Kun Wang1 | Juntao Li1,3 | Wei Xu3 | Haoran Liu3 | Kexi Yang1,3 | Jinghan Zhu1,2,3 | Jiayu Wang1 | Qinhua Xi3 | Tongguo Shi1 | Rui Li2,3 1Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, China 2Jiangsu Key Laboratory of Clinical Immunology, Soochow University, Suzhou, China 3 Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China Correspondence Tongguo Shi, Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, 178 East Ganjiang Rd, Suzhou 215000, China. Email: [shitg@suda.edu.cn](shitg@suda.edu.cn) Rui Li, Department of Gastroenterology, The First Affiliated Hospital of Soochow University, 188, Shizi Rd, Suzhou, Jiangsu 215000, China. Email: [lrhcsz@163.com](lrhcsz@163.com) Funding information Key Project of Medical Research of Jiangsu Commission of Health, Grant/ Award Number: ZDA2020008; Suzhou Special Project on Clinical Key Diseases Treatment Technology of Suzhou Commission of Health, Grant/ Award Number: LCZX201803; iangsu Provincial Medical Key Discipline (No. ZDXK202246); the Natural Science Foundation of the Jiangsu Higher Education Institutions of China iangsu Provincial Medical Key Discipline (No. ZDXK202246); the Natural Science Foundation of the Jiangsu Higher Education Institutions of China, Grant/ Award Number: 20KJA310005; People's Livelihood and Science and Technology project of Department of Science and Technology of Suzhou, Grant/Award Number: SS2019059; Suzhou “Science and Education Revitalize Health” Youth Science and Technology Project, Grant/ Award Number: KJXW2022005 Abstract The resistance to anoikis plays a critical role in the metastatic progression of various types of malignancies, including gastric cancer (GC) . Nevertheless, the precise mechanism behind anoikis resistance is not fully understood. Here, our primary focus was to examine the function and underlying molecular mechanism of Integrin beta-like 1 (ITGBL1) in the modulation of anoikis resistance and metastasis in GC. The findings of our investigation have demonstrated that the overexpression of ITGBL1 significantly augmented the resistance of GC cells to anoikis and promoted their metastatic potential, while knockdown of ITGBL1 had a suppressive effect on both cellular processes in vitro and in vivo. Mechanistically, we proved that ITGBL1 has a role in enhancing the resistance of GC cells to anoikis and promoting metastasis through the AKT/Fibulin-2 (FBLN2) axis. The inhibition of AKT/FBLN2 signalling was able to reverse the impact of ITGBL1 on the resistance of GC cells to anoikis and their metastatic capability. Moreover, the expression levels of ITGBL1 were found to be significantly elevated in the cancerous tissues of patients diagnosed with GC, and there was a strong correlation observed between high expression levels of ITGBL1 and worse prognosis among individuals diagnosed with GC. Significantly, it was revealed that within our cohort of GC patients, individuals exhibiting elevated ITGBL1 expression and diminished FBLN2 expression experienced the worst prognosis. In conclusion, the findings of our study indicate that ITGBL1 may serve as a possible modulator of resistance to anoikis and the metastatic process in GC. K E Y WO R D S anoikis, FBLN2, gastric cancer, ITGBL1, metastasis | Kanger Shen, Wei Xia, Kun Wang have contributed equally to this study. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine a

FAQs

What role does ITGBL1 play in gastric cancer cells regarding anoikis?

ITGBL1 overexpression increases gastric cancer cell resistance to anoikis, while ITGBL1 knockdown suppresses anoikis-related processes in vitro and in vivo.

How does the AKT/FBLN2 axis relate to ITGBL1-driven effects?

The study shows ITGBL1 promotes anoikis resistance and metastasis through the AKT/FBLN2 axis; inhibiting AKT/FBLN2 reverses the effects of ITGBL1 on anoikis resistance and metastatic ability.

Is ITGBL1 clinically associated with prognosis in gastric cancer patients?

ITGBL1 expression is significantly elevated in cancerous gastric tissues and correlates with worse prognosis. Patients with higher ITGBL1 and lower FBLN2 expression show the poorest outcomes.

Sep 21, 2026

Uploaded by Himbo