Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

24 April 2019 : Laboratory Research  

Osteopontin Promotes Colorectal Cancer Cell Invasion and the Stem Cell-Like Properties through the PI3K-AKT-GSK/3β-β/Catenin Pathway

Yuanguang Cheng12BCDEF, Gang Wen2CDEF, Yong Sun2CDEF, Yang Shen2BC, Yongqing Zeng2EF, Ming Du2BCD, Guangyu Zhu2CD, Guanglong Wang2BCD, Xiangling Meng1ABCFG*

DOI: 10.12659/MSM.913185

Med Sci Monit 2019; 25:3014-3025

Abstract

BACKGROUND: Osteopontin (OPN) is a molecule expressed in numerous cancers including colorectal cancer (CRC) that correlates disease progression. The interaction of OPN that promotes CRC cell migration, invasion, and cancer stem-like cells (CSCs) have not been elucidated. Hence, we aimed to investigate the mechanisms that might be involved.

MATERIAL AND METHODS: Expression of OPN in tumor tissues derived from patients was monitored with real-time quantitative polymerase chain reaction and western blot. Wound healing and Transwell assay were used to test the differences in migration and invasion in an OPN enriched environment and OPN knockdown condition. Aldehyde dehydrogenase 1 (ALDH1) positive stem cells were isolated using fluorescence-activated cell sorting (FACS) following the protocol of the ALDEFLUOR™ kit. The expression of protein participation in the PI3K-Akt-GSK/3β-β/catenin pathway was detected by western blot.

RESULTS: OPN exhibited increased levels in CRC tumor tissue compared with non-tumor normal tissue and the high level of which correlated with lymphatic metastasis and late TNM stage. Additional rhOPN co-cultured low-expression CRC cells demonstrated more aggressive capability of proliferation, migration, and invasion. For knockdown of OPN in high-expression CRC cells, the bioactivities of proliferation, migration, and invasion were significantly inhibited. Interestingly, the percentage of ALDH1 labeled stem cells was dramatically decreased by OPN inhibition. The phosphorylation of PI3K-Akt-GSK/3β-β/catenin pathway was involved in the OPN signaling. Furthermore, Ly294002, a specific PI3K inhibitor, can reverse the promotion of bioactivities and stem cell proportion among rhOPN treated CRC cells.

CONCLUSIONS: OPN promoted cell proliferation, migration, and invasion, and was accompanied by upregulation of ALDH1-positive CSC in CRC through activation of PI3K-Akt-GSK/3β-β/catenin pathway.

Keywords: Colorectal Neoplasms, Osteopontin, Transcellular Cell Migration, glycogen synthase kinase 3 beta, Neoplastic Stem Cells, Real-Time Polymerase Chain Reaction, beta Catenin

Add Comment 0 Comments

Editorial

01 February 2025 : Editorial  

Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-Smokers

Dinah V. Parums

DOI: 10.12659/MSM.948255

Med Sci Monit 2025; 31:e948255

0:00

In Press

Clinical Research  

Pre- and Post-Surgical MRI Analysis of Levator Ani in Pelvic Organ Prolapse Patients: A Single-Center Study

Med Sci Monit In Press; DOI: 10.12659/MSM.945993  

Clinical Research  

Comparative Impact of Kinesio Taping and Post-Isometric Muscle Relaxation on Pain and Myofascial Mechanics ...

Med Sci Monit In Press; DOI: 10.12659/MSM.945376  

Clinical Research  

Surgical Efficacy in Varicocele Ligation with Ephedrine-Assisted Blood Pressure Control

Med Sci Monit In Press; DOI: 10.12659/MSM.946234  

Clinical Research  

Retrospective Study to Compare Injury Patterns and Associations in 170 Patients Following Electric Scooter ...

Med Sci Monit In Press; DOI: 10.12659/MSM.947155  

Most Viewed Current Articles

17 Jan 2024 : Review article   6,968,277

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

16 May 2023 : Clinical Research   701,791

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Mar 2024 : Editorial   25,442

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...

DOI :10.12659/MSM.944204

Med Sci Monit 2024; 30:e944204

0:00

28 Jan 2024 : Review article   20,020

A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and Future

DOI :10.12659/MSM.943912

Med Sci Monit 2024; 30:e943912

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750