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, Phosphatidylinositol 3-Kinases, Transcellular Cell Migration, Disease Progression, glycogen synthase kinase 3 beta, Neoplastic Stem Cells, Proto-Oncogene Proteins c-akt, Real-Time Polymerase Chain Reaction, beta Catenin

Add Comment 0 Comments

Editorial

01 April 2024 : Editorial  

Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug Resistance

Dinah V. Parums

DOI: 10.12659/MSM.944600

Med Sci Monit 2024; 30:e944600

0:00

In Press

05 Apr 2024 : Clinical Research  

Comparative Analysis of Transoral Endoscopic Parathyroidectomy Vestibular Approach and Focused Open Surgery...

Med Sci Monit In Press; DOI: 10.12659/MSM.944128  

0:00

05 Mar 2024 : Clinical Research  

Muscular Function Recovery from General Anesthesia in 132 Patients Undergoing Surgery with Acceleromyograph...

Med Sci Monit In Press; DOI: 10.12659/MSM.942780  

05 Mar 2024 : Clinical Research  

Effects of Thermal Insulation on Recovery and Comfort of Patients Undergoing Holmium Laser Lithotripsy

Med Sci Monit In Press; DOI: 10.12659/MSM.942836  

05 Mar 2024 : Clinical Research  

Role of Critical Shoulder Angle in Degenerative Type Rotator Cuff Tears: A Turkish Cohort Study

Med Sci Monit In Press; DOI: 10.12659/MSM.943703  

Most Viewed Current Articles

17 Jan 2024 : Review article  

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

14 Dec 2022 : Clinical Research  

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research  

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 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

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