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

被引：14

作者：

Sadrkhanloo, Mehrdokht ^{[1
]}

Paskeh, Mahshid Deldar Abad ^{[2
,3
]}

Hashemi, Mehrdad ^{[2
,3
]}

Raesi, Rasoul ^{[4
,5
]}

Bahonar, Alireza ^{[6
]}

Nakhaee, Zahra ^{[7
]}

Entezari, Maliheh ^{[2
,3
]}

Goharrizi, Mohammad Ali Sheikh Beig ^{[8
]}

Salimimoghadam, Shokooh ^{[9
]}

Ren, Jun ^{[10
]}

Nabavi, Noushin ^{[11
]}

Rashidi, Mohsen ^{[12
,13
]}

Dehkhoda, Farshid ^{[14
]}

Taheriazam, Afshin ^{[3
,15
]}

Tan, Shing Cheng ^{[16
]}

Hushmandif, Kiavash ^{[6
]}

机构：

[1] Islamic Azad Univ, Fac Med, Tehran Med Sci, Tehran, Iran

[2] Islamic Azad Univ, Fac Adv Sci & Technol, Dept Genet, Tehran Med Sci, Tehran, Iran

[3] Islamic Azad Univ, Farhikhtegan Hosp Tehran Med Sci, Farhikhtegan Med Convergence Sci Res Ctr, Tehran, Iran

[4] Mashhad Univ Med Sci, Dept Hlth Serv Management, Mashhad, Iran

[5] Mashhad Univ Med Sci, Dept Med Surg Nursing, Mashhad, Iran

[6] Univ Tehran, Fac Vet Med, Dept Food Hyg & Qual Control, Div Epidemiol, Tehran, Iran

[7] Gonabad Univ Med Sci, Med Sch, Gonabad, Iran

[8] Univ Tehran, Fac Biotechnol, Tehran, Iran

[9] Shahid Chamran Univ Ahvaz, Fac Vet Med, Dept Biochem & Mol Biol, Ahvaz, Iran

[10] Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Dept Cardiol, Shanghai 200032, Peoples R China

[11] Univ British Columbia, Vancouver Prostate Ctr, Dept Urol Sci, Vancouver, BC V6H3Z6, Canada

[12] Mazandaran Univ Med Sci, Fac Med, Dept Pharmacol, Sari, Iran

[13] Mazandaran Univ Med Sci, Hlth Plant & Livestock Prod Res Ctr, Sari, Iran

[14] Shahid Beheshti Univ Med Sci, Imam Hossein Hosp, Dept Orthoped, Tehran, Iran

[15] Islamic Azad Univ, Tehran Med Sci, Fac Med, Dept Orthoped, Tehran, Iran

[16] Univ Kebangsaan Malaysia, UKM Med Mol Biol Inst, Kuala Lumpur, Malaysia

来源：

PATHOLOGY RESEARCH AND PRACTICE | 2023年 / 251卷

关键词：

Osteosarcoma; PI3K/Akt; PTEN; Gene therapy; Resistant; Non-coding RNAs; PROMOTES CELL-PROLIFERATION; DOWN-REGULATION; CISPLATIN RESISTANCE; SIGNALING PATHWAY; WNT/BETA-CATENIN; TUMOR-GROWTH; SUPPRESSES PROLIFERATION; MESENCHYMAL TRANSITION; INHIBITS PROLIFERATION; ENDOMETRIAL CANCER;

D O I：

10.1016/j.prp.2023.154902

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The het-erogeneous 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 treat-ments 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 re-ported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and down-regulation 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.

引用

页数：15

共 267 条

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