Logo Medical Science Monitor Basic Research

Call: 1.631.470.9640
Mon-Fri 10 am - 2 pm EST

Contact Us

Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research Logo Medical Science Monitor Basic Research

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, Neoplasm Metastasis, Osteopontin, Phosphatidylinositol 3-Kinases, Transcellular Cell Migration, Aged, Apoptosis, Cell Differentiation, Cell Movement, Cell Proliferation, Disease Progression, glycogen synthase kinase 3 beta, Middle Aged, Neoplasm Invasiveness, Neoplastic Stem Cells, Proto-Oncogene Proteins c-akt, Real-Time Polymerase Chain Reaction, Signal Transduction, beta Catenin

0 Comments

Most Viewed Current Articles

13 Apr 2020 : Original article  

Outcome of 24 Weeks of Combined Schroth and Pilates Exercises on Cobb Angle, Angle of Trunk Rotation, Chest...

DOI :10.12659/MSMBR.920449

Med Sci Monit Basic Res 2020; 26:e920449

11 May 2020 : Original article  

Analysis of Psychological and Sleep Status and Exercise Rehabilitation of Front-Line Clinical Staff in the ...

DOI :10.12659/MSMBR.924085

Med Sci Monit Basic Res 2020; 26:e924085

05 Jan 2021 : Review article  

A Southeast Asian Perspective on the COVID-19 Pandemic: Hemoglobin E (HbE)-Trait Confers Resistance Against...

DOI :10.12659/MSMBR.929207

Med Sci Monit Basic Res 2021; 27:e929207

10 Aug 2020 : Clinical Research  

Effects of Cognitive Task Training on Dynamic Balance and Gait of Patients with Stroke: A Preliminary Rando...

DOI :10.12659/MSMBR.925264

Med Sci Monit Basic Res 2020; 26:e925264

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 Basic Research eISSN: 2325-4416
Medical Science Monitor Basic Research eISSN: 2325-4416