New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis

Sadrkhanloo M 1 , Paskeh MDA 2 , Hashemi M 2 , Raesi R 3 , Bahonar A 4 , Nakhaee Z 5 Show all authors , Entezari M 2 , Beig Goharrizi MAS 6 , Salimimoghadam S 7 , Ren J 8 , Nabavi N 9 , Rashidi M 10 , Dehkhoda F 11 , Taheriazam A 12 , Tan SC 13 , Hushmandi K 14

Affiliations 

  • 1 Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • 2 Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • 3 Department of Health Services Management, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical-Surgical Nursing, Mashhad University of Medical Sciences, Mashhad, Iran
  • 4 Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  • 5 Medical School, Gonabad University of Medical Sciences, Gonabad, Iran
  • 6 Faculty of Biotechnology, University of Tehran, Tehran, Iran
  • 7 Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
  • 8 Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
  • 9 Department of Urologic Sciences and Vancouver Prostate Centre, University of British Columbia, V6H3Z6 Vancouver, BC, Canada
  • 10 Department Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address: dr.mohsenrashidi@yahoo.com
  • 11 Department of Orthopedics, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: dehkhoda@sbmu.ac.ir
  • 12 Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Orthopedics, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran. Electronic address: a.taheriazam@iautmu.ac.ir
  • 13 UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
  • 14 Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran. Electronic address: Houshmandi.kia7@ut.ac.ir
Pathol Res Pract, 2023 Nov;251:154902.
PMID: 37922723 DOI: 10.1016/j.prp.2023.154902

Abstract

Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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