Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2022

Open Access 01-12-2022 | Review

Role of PI3K/AKT pathway in squamous cell carcinoma with an especial focus on head and neck cancers

Authors: Soudeh Ghafouri-Fard, Ali Noie Alamdari, Yashar Noee Alamdari, Atefe Abak, Bashdar Mahmud Hussen, Mohammad Taheri, Elena Jamali

Published in: Cancer Cell International | Issue 1/2022

Login to get access

Abstract

PI3K/AKT pathway is an important pathway in the carcinogenesis since it has central impacts in the regulation of metabolic pathways, cell proliferation and survival, gene expression and protein synthesis. This pathway has been reported to be dysregulated in several types of cancers. In the current review, we summarize the role of this signaling pathway in squamous cell carcinomas (SCCs) originated from different parts of body cervix, oral cavity, head and neck and skin. The data presented in the current review shows the impact of dysregulation of PI3K/AKT pathway in survival of patients with SCC. Moreover, targeted therapies against this pathway have been found to be effective in reduction of tumor burden both in animal models and clinical settings. Finally, a number of molecules that regulate PI3K/AKT pathway can be used as diagnostic markers for different types of SCCs.
Literature
1.
Jiang N, Dai Q, Su X, Fu J, Feng X, Peng J. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior. Mol Biol Rep. 2020;47(6):4587–629.PubMedPubMedCentralCrossRef
2.
Fayard E, Moncayo G, Hemmings BA, Holländer GA. Phosphatidylinositol 3-kinase signaling in thymocytes the need for stringent control. Sci Signal. 2010;3(135):re5-re.PubMedCrossRef
3.
4.
Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, et al. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 1996;15(23):6541–51.PubMedPubMedCentralCrossRef
5.
Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005;307(5712):1098–101.PubMedCrossRef
6.
Hou M-M, Liu X, Wheler J, Naing A, Hong D, Coleman RL, et al. Targeted PI3K/AKT/mTOR therapy for metastatic carcinomas of the cervix: a phase I clinical experience. Oncotarget. 2014;5(22):11168–79.PubMedPubMedCentralCrossRef
7.
Srinivas KP, Viji R, Dan VM, Sajitha IS, Prakash R, Rahul PV, et al. DEPTOR promotes survival of cervical squamous cell carcinoma cells and its silencing induces apoptosis through downregulating PI3K/AKT and by up-regulating p38 MAP kinase. Oncotarget. 2016;7(17):24154–71.PubMedPubMedCentralCrossRef
8.
Li R, Song Y, Zhou L, Li W, Zhu X. Downregulation of RAGE inhibits cell proliferation and induces apoptosis via regulation of PI3K/AKT pathway in cervical squamous cell carcinoma. Onco Targets Ther. 2020;13:2385.PubMedPubMedCentralCrossRef
9.
Prasad SB, Yadav SS, Das M, Modi A, Kumari S, Pandey LK, et al. PI3K/AKT pathway-mediated regulation of p27Kip1 is associated with cell cycle arrest and apoptosis in cervical cancer. Cell Oncol. 2015;38(3):215–25.CrossRef
10.
Zhang D, Sun G, Zhang H, Tian J, Li Y. Long non-coding RNA ANRIL indicates a poor prognosis of cervical cancer and promotes carcinogenesis via PI3K/Akt pathways. Biomed Pharmacother. 2017;85:511–6.PubMedCrossRef
11.
Wang C, Gu W, Zhang Y, Ji Y, Wen Y, Xu X. Nicotine promotes cervical carcinoma cell line HeLa migration and invasion by activating PI3k/Akt/NF-κB pathway in vitro. Exp Toxicol Pathol. 2017;69(6):402–7.PubMedCrossRef
12.
Shu X-R, Wu J, Sun H, Chi L-Q, Wang J-H. PAK4 confers the malignance of cervical cancers and contributes to the cisplatin-resistance in cervical cancer cells via PI3K/AKT pathway. Diagn Pathol. 2015;10(1):177.PubMedPubMedCentralCrossRef
13.
Feng T, Zheng L, Liu F, Xu X, Mao S, Wang X, et al. Growth factor progranulin promotes tumorigenesis of cervical cancer via PI3K/Akt/mTOR signaling pathway. Oncotarget. 2016;7(36):58381–95.PubMedPubMedCentralCrossRef
14.
Huang L, Huang Z, Fan Y, He L, Ye M, Shi K, et al. FOXC1 promotes proliferation and epithelial-mesenchymal transition in cervical carcinoma through the PI3K-AKT signal pathway. Am J Transl Res. 2017;9(3):1297–306.PubMedPubMedCentral
15.
Zhang W, Zhou Q, Wei Y, Da M, Zhang C, Zhong J, et al. The exosome-mediated PI3k/Akt/mTOR signaling pathway in cervical cancer. Int J Clin Exp Pathol. 2019;12(7):2474–84.PubMedPubMedCentral
16.
Tsai J-P, Lee C-H, Ying T-H, Lin C-L, Lin C-L, Hsueh J-T, et al. Licochalcone A induces autophagy through PI3K/Akt/mTOR inactivation and autophagy suppression enhances Licochalcone A-induced apoptosis of human cervical cancer cells. Oncotarget. 2015;6(30):28851–66.PubMedPubMedCentralCrossRef
17.
Li A, Gu Y, Li X, Sun H, Zha H, Xie J, et al. S100A6 promotes the proliferation and migration of cervical cancer cells via the PI3K/Akt signaling pathway. Oncol Lett. 2018;15(4):5685–93.PubMedPubMedCentral
18.
Xu J, Zhu W, Chen L, Liu L. MicroRNA-433 inhibits cell growth and induces apoptosis in human cervical cancer through PI3K/AKT signaling by targeting FAK. Oncol Rep. 2018;40(6):3469–78.PubMed
19.
Lu R, Yang Z, Xu G, Yu S. miR-338 modulates proliferation and autophagy by PI3K/AKT/mTOR signaling pathway in cervical cancer. Biomed Pharmacother. 2018;105:633–44.PubMedCrossRef
20.
Li L, Huizhi L, Binu W, Xinxin D, Longjun W, Liping Y, et al. Anticancer activity of mukonal against human laryngeal cancer cells involves apoptosis, cell cycle arrest, and inhibition of PI3K/AKT and MEK/ERK signalling pathways. Med Sci Monit. 2018;24:7295.PubMedPubMedCentralCrossRef
21.
Zhang R, Hao J, Wu Q, Guo K, Wang C, Zhang WK, et al. Dehydrocostus lactone inhibits cell proliferation and induces apoptosis by PI3K/Akt/Bad and ERS signalling pathway in human laryngeal carcinoma. J Cell Mol Med. 2020;24(11):6028–42.PubMedPubMedCentralCrossRef
22.
Starska K, Forma E, Lewy-Trenda I, Stasikowska-Kanicka O, Skóra M, Bryś M. Fibroblast growth factor receptor 1 and 3 expression is associated with regulatory PI3K/AKT kinase activity, as well as invasion and prognosis, in human laryngeal cancer. Cell Oncol. 2018;41(3):253–68.CrossRef
23.
Zhao R, Tian L, Zhao B, Sun Y, Cao J, Chen K, et al. FADS1 promotes the progression of laryngeal squamous cell carcinoma through activating AKT/mTOR signaling. Cell Death Dis. 2020;11(4):1–14.CrossRef
24.
Gao W, Guo H, Niu M, Zheng X, Zhang Y, Xue X, et al. circPARD3 drives malignant progression and chemoresistance of laryngeal squamous cell carcinoma by inhibiting autophagy through the PRKCI-Akt-mTOR pathway. Mol Cancer. 2020;19(1):1–22.CrossRef
25.
Gao W, Zhang Y, Luo H, Niu M, Zheng X, Hu W, et al. Targeting SKA3 suppresses the proliferation and chemoresistance of laryngeal squamous cell carcinoma via impairing PLK1–AKT axis-mediated glycolysis. Cell Death Dis. 2020;11(10):1–19.CrossRef
26.
Tang T, Xiao Z-Y, Shan G, Lei H-B. Descending-SHIP2-mediated radiosensitivity enhancement through PI3K/Akt signaling pathway in laryngeal squamous cell carcinoma. Biomed Pharmacother. 2019;118: 109392.PubMedCrossRef
27.
Ye D, Zhou C, Deng H, Lin L, Zhou S. MicroRNA-145 inhibits growth of laryngeal squamous cell carcinoma by targeting the PI3K/Akt signaling pathway. Cancer Manag Res. 2019;11:3801.PubMedPubMedCentralCrossRef
28.
Zhu Y, Yan L, Zhu W, Song X, Yang G, Wang S. MMP2/3 promote the growth and migration of laryngeal squamous cell carcinoma via PI3K/Akt-NF-κB-mediated epithelial–mesenchymal transformation. J Cell Physiol. 2019;234(9):15847–55.CrossRef
29.
Tian L, Tao Z, Ye H, Li G, Zhan Z, Tuo H. Over-expression of MEOX2 promotes apoptosis through inhibiting the PI3K/Akt pathway in laryngeal cancer cells. Neoplasma. 2018;65(5):745–52.PubMedCrossRef
30.
Ni HS, Hu SQ, Chen X, Liu YF, Ni TT, Cheng L. Tra2β silencing suppresses cell proliferation in laryngeal squamous cell carcinoma via inhibiting PI3K/AKT signaling. Laryngoscope. 2019;129(9):E318–28.PubMedCrossRef
31.
Zhu X, Zhu R. Curcumin suppresses the progression of laryngeal squamous cell carcinoma through the upregulation of miR-145 and inhibition of the PI3K/Akt/mTOR pathway. Onco Targets Ther. 2018;11:3521.PubMedPubMedCentralCrossRef
32.
Si F, Sun J, Wang C. MicroRNA-138 suppresses cell proliferation in laryngeal squamous cell carcinoma via inhibiting EZH2 and PI3K/AKT signaling. Exp Ther Med. 2017;14(3):1967–74.PubMedPubMedCentralCrossRef
33.
Wang B, Lv K, Chen W, Zhao J, Luo J, Wu J, et al. miR-375 and miR-205 regulate the invasion and migration of laryngeal squamous cell carcinoma synergistically via AKT-mediated EMT. BioMed Res Int. 2016;2016:11.CrossRef
34.
Lian R, Lu B, Jiao L, Li S, Wang H, Miao W, et al. MiR-132 plays an oncogenic role in laryngeal squamous cell carcinoma by targeting FOXO1 and activating the PI3K/AKT pathway. Eur J Pharmacol. 2016;792:1–6.PubMedCrossRef
35.
Zhu H, Lv Z, An C, Shi M, Pan W, Zhou L, et al. Onco-lncRNA HOTAIR and its functional genetic variants in papillary thyroid carcinoma. Sci Rep. 2016;23(6):31969.CrossRef
36.
Wang B, Qin H, Wang Y, Chen W, Luo J, Zhu X, et al. Effect of DJ-1 overexpression on the proliferation, apoptosis, invasion and migration of laryngeal squamous cell carcinoma SNU-46 cells through PI3K/AKT/mTOR. Oncol Rep. 2014;32(3):1108–16.PubMedCrossRef
37.
Lu B, Di W, Wang H, Ma H, Li J, Zhang Q. Tumor suppressor TSLC1 is implicated in cell proliferation, invasion and apoptosis in laryngeal squamous cell carcinoma by regulating Akt signaling pathway. Tumor Biol. 2012;33(6):2007–17.CrossRef
38.
Yang Y-F, Feng L, Shi Q, Ma H-Z, He S-Z, Hou L-Z, et al. Silencing novel long non-coding RNA FKBP9P1 represses malignant progression and inhibits PI3K/AKT signaling of head and neck squamous cell carcinoma in vitro. Chin Med J. 2020;133(17):2037.PubMedPubMedCentralCrossRef
39.
Zhou K, Chen J, Wu J, Xu Y, Wu Q, Yue J, et al. Profilin 2 promotes proliferation and metastasis of head and neck cancer cells by regulating pi3k/akt/β-catenin signaling pathway. Oncol Res. 2019;27(9):1079–88.PubMedPubMedCentralCrossRef
40.
Katase N, Nishimatsu SI, Yamauchi A, Yamamura M, Fujita S. DKK3 knockdown confers negative effects on the malignant potency of head and neck squamous cell carcinoma cells via the PI3K/Akt and MAPK signaling pathways. Int J Oncol. 2019;54(3):1021–32.PubMed
41.
Yang J, Zhu X-J, Jin M-Z, Cao Z-W, Ren Y-Y, Gu Z-W. Osthole induces cell cycle arrest and apoptosis in head and neck squamous cell carcinoma by suppressing the PI3K/AKT signaling pathway. Chem Biol Interact. 2020;316:108934.PubMedCrossRef
42.
Shayan G, Srivastava R, Li J, Schmitt N, Kane LP, Ferris RL. Adaptive resistance to anti-PD1 therapy by Tim-3 upregulation is mediated by the PI3K-Akt pathway in head and neck cancer. Oncoimmunology. 2017;6(1): e1261779.PubMedCrossRef
43.
Bernard M, Cardin GB, Cahuzac M, Ayad T, Bissada E, Guertin L, et al. Dual inhibition of autophagy and PI3K/AKT/MTOR pathway as a therapeutic strategy in head and neck squamous cell carcinoma. Cancers. 2020;12(9):2371.PubMedCentralCrossRef
44.
Yang S, Ji Q, Chang B, Wang Y, Zhu Y, Li D, et al. STC2 promotes head and neck squamous cell carcinoma metastasis through modulating the PI3K/AKT/Snail signaling. Oncotarget. 2017;8(4):5976.PubMedCrossRef
45.
Lee S, Kopp F, Chang T-C, Sataluri A, Chen B, Sivakumar S, et al. Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins. Cell. 2016;164(1–2):69–80.PubMedCrossRef
46.
Zhu G-C, Yu C-Y, She L, Tan H-L, Li G, Ren S-L, et al. Metadherin regulation of vascular endothelial growth factor expression is dependent upon the PI3K/Akt pathway in squamous cell carcinoma of the head and neck. Medicine. 2015;94(6): e502.PubMedPubMedCentralCrossRef
47.
Wu Y-R, Qi H-J, Deng D-F, Luo Y-Y, Yang S-L. MicroRNA-21 promotes cell proliferation, migration, and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer. Tumor Biol. 2016;37(9):12061–70.CrossRef
48.
Zhu Z, Yu W, Fu X, Sun M, Wei Q, Li D, et al. Phosphorylated AKT1 is associated with poor prognosis in esophageal squamous cell carcinoma. J Exp Clin Cancer Res. 2015;34(1):1–8.CrossRef
49.
Chen J, Lan T, Zhang W, Dong L, Kang N, Zhang S, et al. Platelet-activating factor receptor-mediated PI3K/AKT activation contributes to the malignant development of esophageal squamous cell carcinoma. Oncogene. 2015;34(40):5114–27.PubMedCrossRef
50.
Yang P, Zhao J, Hou L, Yang L, Wu K, Zhang L. Vitamin E succinate induces apoptosis via the PI3K/AKT signaling pathways in EC109 esophageal cancer cells. Mol Med Rep. 2016;14(2):1531–7.PubMedPubMedCentralCrossRef
51.
Chen J, Lan T, Zhang W, Dong L, Kang N, Fu M, et al. Dasatinib enhances cisplatin sensitivity in human esophageal squamous cell carcinoma (ESCC) cells via suppression of PI3K/AKT and Stat3 pathways. Arch Biochem Biophys. 2015;575:38–45.PubMedCrossRef
52.
Zhang W, Lei C, Fan J, Wang J. miR-18a promotes cell proliferation of esophageal squamous cell carcinoma cells by increasing cylin D1 via regulating PTEN-PI3K-AKT-mTOR signaling axis. Biochem Biophys Res Commun. 2016;477(1):144–9.PubMedCrossRef
53.
Tian B, Chen X, Zhang H, Li X, Wang J, Han W, et al. Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma. Oncotarget. 2017;8(26):42300.PubMedPubMedCentralCrossRef
54.
Lu H, Jiang T, Ren K, Li ZL, Ren J, Wu G, et al. RUNX2 plays an oncogenic role in esophageal carcinoma by activating the PI3K/AKT and ERK signaling pathways. Cell Physiol Biochem. 2018;49(1):217–25.PubMedCrossRef
55.
Javid H, Asadi J, Avval FZ, Afshari AR, Hashemy SI. The role of substance P/neurokinin 1 receptor in the pathogenesis of esophageal squamous cell carcinoma through constitutively active PI3K/Akt/NF-κB signal transduction pathways. Mol Biol Rep. 2020;47(3):2253–63.PubMedCrossRef
56.
Zhang H-F, Alshareef A, Wu C, Li S, Jiao J-W, Cao H-H, et al. Loss of miR-200b promotes invasion via activating the Kindlin-2/integrin β1/AKT pathway in esophageal squamous cell carcinoma: an E-cadherin-independent mechanism. Oncotarget. 2015;6(30):28949.PubMedPubMedCentralCrossRef
57.
Wu N, Du Z, Zhu Y, Song Y, Pang L, Chen Z. The expression and prognostic impact of the PI3K/AKT/mTOR signaling pathway in advanced esophageal squamous cell carcinoma. Technol Cancer Res Treat. 2018;17:1533033818758772.PubMedPubMedCentralCrossRef
58.
Kodama T, Koma Y-I, Arai N, Kido A, Urakawa N, Nishio M, et al. CCL3–CCR5 axis contributes to progression of esophageal squamous cell carcinoma by promoting cell migration and invasion via Akt and ERK pathways. Lab Invest. 2020;100(9):1140–57.PubMedPubMedCentralCrossRef
59.
Xi R, Pan S, Chen X, Hui B, Zhang L, Fu S, et al. HPV16 E6–E7 induces cancer stem-like cells phenotypes in esophageal squamous cell carcinoma through the activation of PI3K/Akt signaling pathway in vitro and in vivo. Oncotarget. 2016;7(35):57050.PubMedPubMedCentralCrossRef
60.
Peng X, Liu Y, Zhu S, Peng X, Li H, Jiao W, et al. Co-targeting PI3K/Akt and MAPK/ERK pathways leads to an enhanced antitumor effect on human hypopharyngeal squamous cell carcinoma. J Cancer Res Clin Oncol. 2019;145(12):2921–36.PubMedCrossRef
61.
Hsu C-M, Lin P-M, Tsai Y-T, Tsai M-S, Tseng C-H, Lin S-F, et al. NVP-BEZ235, a dual PI3K-mTOR inhibitor, suppresses the growth of FaDu hypopharyngeal squamous cell carcinoma and has a synergistic effect with Cisplatin. Cell Death Discov. 2018;4(1):1–10.CrossRef
62.
Zhang J, An X, Han Y, Ma R, Yang K, Zhang L, et al. Overexpression of JARID1B promotes differentiation via SHIP1/AKT signaling in human hypopharyngeal squamous cell carcinoma. Cell Death Dis. 2016;7(9):e2358-e.PubMedPubMedCentralCrossRef
63.
Wang C, Lin C, Tao Q, Zhao S, Liu H, Li L. Evaluation of calcium-binding protein A11 promotes the carcinogenesis of hypopharygeal squamous cell carcinoma via the PI3K/AKT signaling pathway. Am J Transl Res. 2019;11(6):3472.PubMedPubMedCentral
64.
Zhang Y, Wang B, Chen X, Li W, Dong P. AGO2 involves the malignant phenotypes and FAK/PI3K/AKT signaling pathway in hypopharyngeal-derived FaDu cells. Oncotarget. 2017;8(33):54735.PubMedPubMedCentralCrossRef
65.
Zhang Y, Cong L, He J, Wang Y, Zou Y, Yang Z, et al. Photothermal treatment with EGFRmAb–AuNPs induces apoptosis in hypopharyngeal carcinoma cells via PI3K/AKT/mTOR and DNA damage response pathways. Acta Biochim Biophys Sin. 2018;50(6):567–78.PubMedCrossRef
66.
Horn D, Freudlsperger C, Holzinger D, Kunzmann K, Plinkert P, Dyckhoff G, et al. Upregulation of pAKT (Ser473) expression in progression of HPV-positive oropharyngeal squamous cell carcinoma. Head Neck. 2017;39(12):2397–405.PubMedCrossRef
67.
Won HS, Jung C-K, Chun SH, Kang J-H, Kim Y-S, Sun D-I, et al. Difference in expression of EGFR, pAkt, and PTEN between oropharyngeal and oral cavity squamous cell carcinoma. Oral Oncol. 2012;48(10):985–90.PubMedCrossRef
68.
Choi MS, Moon SM, Lee SA, Park BR, Kim JS, Kim DK, et al. Adenosine induces intrinsic apoptosis via the PI3K/Akt/mTOR signaling pathway in human pharyngeal squamous carcinoma FaDu cells Corrigendum in/https://​doi.​org/​10.​3892/​ol.​2019.​10014. Oncol Lett. 2018;15(5):6489–96.
69.
Wang R, Lu X, Yu R. Lycopene inhibits epithelial-mesenchymal transition and promotes apoptosis in oral cancer via PI3K/AKT/m-TOR signal pathway. Drug Des Dev Ther. 2020;14:2461.CrossRef
70.
Ren X, Luo W. Exploration of pro-apoptotic effect of Thymoquinone on oral squamous cell carcinoma cells through PI3K/Akt signaling pathway. Cell Mol Biol (Noisy-le-grand). 2019;65(1):61–4.CrossRef
71.
Hao Y, Zhang C, Sun Y, Xu H. Licochalcone A inhibits cell proliferation, migration, and invasion through regulating the PI3K/AKT signaling pathway in oral squamous cell carcinoma. Onco Targets Ther. 2019;12:4427.PubMedPubMedCentralCrossRef
72.
Yuan J, Xu X, Lin Y, Chen Q, Sun W, Tang L, et al. LncRNA MALAT1 expression inhibition suppresses tongue squamous cell carcinoma proliferation, migration and invasion by inactivating PI3K/Akt pathway and downregulating MMP-9 expression. Eur Rev Med Pharmacol Sci. 2019;23(1):198–206.PubMed
73.
Li Z, Liu J, Que L, Tang X. The immunoregulatory protein B7–H3 promotes aerobic glycolysis in oral squamous carcinoma via PI3K/Akt/mTOR pathway. J Cancer. 2019;10(23):5770.PubMedPubMedCentralCrossRef
74.
Li C, Lin X, Wang J, Ren X. FBXW7 inhibited cell proliferation and invasion regulated by miR-27a through PI3K/AKT signaling pathway and epithelial-to-mesenchymal transition in oral squamous cell carcinoma. Eur Rev Med Pharmacol Sci. 2020;24(7):3701–9.PubMed
75.
Wang H, Wang L, Zhou X, Luo X, Liu K, Jiang E, et al. OSCC exosomes regulate miR-210–3p targeting EFNA3 to promote oral cancer angiogenesis through the PI3K/AKT pathway. BioMed Res Int. 2020;2020:13.
76.
Fan Q-C, Tian H, Wang Y, Liu X-B. Integrin-α5 promoted the progression of oral squamous cell carcinoma and modulated PI3K/AKT signaling pathway. Arch Oral Biol. 2019;101:85–91.PubMedCrossRef
77.
Jing Y, Jin Y, Wang Y, Chen S, Zhang X, Song Y, et al. SPARC promotes the proliferation and metastasis of oral squamous cell carcinoma by PI3K/AKT/PDGFB/PDGFRβ axis. J Cell Physiol. 2019;234(9):15581–93.CrossRef
78.
Kowshik J, Nivetha R, Ranjani S, Venkatesan P, Selvamuthukumar S, Veeravarmal V, et al. Astaxanthin inhibits hallmarks of cancer by targeting the PI3K/NF-κΒ/STAT3 signalling axis in oral squamous cell carcinoma models. IUBMB Life. 2019;71(10):1595–610.PubMedCrossRef
79.
Liu C, Tong Z, Tan J, Xin Z, Wang Z, Tian L. MicroRNA-21-5p targeting PDCD4 suppresses apoptosis via regulating the PI3K/AKT/FOXO1 signaling pathway in tongue squamous cell carcinoma. Exp Ther Med. 2019;18(5):3543–51.PubMedPubMedCentral
80.
Liu H, Gong X, Yang K. Overexpression of the clock gene Per2 suppresses oral squamous cell carcinoma progression by activating autophagy via the PI3K/AKT/mTOR pathway. J Cancer. 2020;11(12):3655.PubMedPubMedCentralCrossRef
81.
Qu Z, Zhang R, Su M, Liu W. USP13 serves as a tumor suppressor via the PTEN/AKT pathway in oral squamous cell carcinoma. Cancer Manag Res. 2019;11:9175.PubMedPubMedCentralCrossRef
82.
Guo L, Yang G, Kang Y, Li S, Duan R, Shen L, et al. Construction and analysis of a ceRNA network reveals potential prognostic markers in colorectal cancer. Front Genet. 2020;11:418.PubMedPubMedCentralCrossRef
83.
84.
Tang G, Tang Q, Jia L, Chen Y, Lin L, Kuai X, et al. TROP2 increases growth and metastasis of human oral squamous cell carcinoma through activation of the PI3K/Akt signaling pathway. Int J Mol Med. 2019;44(6):2161–70.PubMedPubMedCentral
85.
Tomita R, Sasabe E, Tomomura A, Yamamoto T. Macrophage-derived exosomes attenuate the susceptibility of oral squamous cell carcinoma cells to chemotherapeutic drugs through the AKT/GSK-3β pathway. Oncol Rep. 2020;44(5):1905–16.PubMedPubMedCentral
86.
Tsai C-N, Tsai C-L, Yi J-S, Kao H-K, Huang Y, Wang C-I, et al. Activin A regulates the epidermal growth factor receptor promoter by activating the PI3K/SP1 pathway in oral squamous cell carcinoma cells. Sci Rep. 2019;9(1):1–14.
87.
Velu P, Vijayalakshmi A, Vinothkumar V. Inhibiting the PI3K/Akt, NF-κB signalling pathways with syringic acid for attenuating the development of oral squamous cell carcinoma cells SCC131. J Pharm Pharmacol. 2020;72(11):1595–606.PubMedCrossRef
88.
Wang H, Wu B, Wang H. Alpha-hederin induces the apoptosis of oral cancer SCC-25 cells by regulating PI3K/Akt/mTOR signaling pathway. Electron J Biotechnol. 2019;38:27–31.CrossRef
89.
Wang L, Song Y, Wang H, Liu K, Shao Z, Shang Z. MiR-210-3p-EphrinA3-PI3K/AKT axis regulates the progression of oral cancer. J Cell Mol Med. 2020;24(7):4011–22.PubMedPubMedCentralCrossRef
90.
Wang J, Jiang C, Li N, Wang F, Xu Y, Shen Z, et al. The circEPSTI1/mir-942-5p/LTBP2 axis regulates the progression of OSCC in the background of OSF via EMT and the PI3K/Akt/mTOR pathway. Cell Death Dis. 2020;11(8):1–18.PubMedPubMedCentralCrossRef
91.
Wei M, Wu Y, Liu H, Xie C. Genipin induces autophagy and suppresses cell growth of oral squamous cell carcinoma via PI3K/AKT/MTOR pathway. Drug Des Dev Ther. 2020;14:395.CrossRef
92.
Wu H, Li L, Ai Z, Yin J, Chen L. Pristimerin induces apoptosis of oral squamous cell carcinoma cells via G1 phase arrest and MAPK/Erk1/2 and Akt signaling inhibition. Oncol Lett. 2019;17(3):3017–25.PubMedPubMedCentral
93.
Wu J, Wang X, Shang A, Vella G, Sun Z, Ji P, et al. PLAC8 inhibits oral squamous cell carcinogenesis and epithelial-mesenchymal transition via the Wnt/β-catenin and PI3K/Akt/GSK3β signaling pathways. Oncol Lett. 2020;20(5):1.
94.
Yang Y, Chen D, Liu H, Yang K. Increased expression of lncRNA CASC9 promotes tumor progression by suppressing autophagy-mediated cell apoptosis via the AKT/mTOR pathway in oral squamous cell carcinoma. Cell Death Dis. 2019;10(2):1–16.CrossRef
95.
Yang G, Yang Y, Tang H, Yang K. Loss of the clock gene Per1 promotes oral squamous cell carcinoma progression via the AKT/mTOR pathway. Cancer Sci. 2020;111(5):1542.PubMedPubMedCentralCrossRef
96.
Zhang X, Ding H, Lu Z, Ding L, Song Y, Jing Y, et al. Increased LGALS3BP promotes proliferation and migration of oral squamous cell carcinoma via PI3K/AKT pathway. Cell Signal. 2019;63: 109359.PubMedCrossRef
97.
Zheng Y, Wang Z, Xiong X, Zhong Y, Zhang W, Dong Y, et al. Membrane-tethered Notch1 exhibits oncogenic property via activation of EGFR–PI3K–AKT pathway in oral squamous cell carcinoma. J Cell Physiol. 2019;234(5):5940–52.PubMedCrossRef
98.
99.
Liu M, Gao X, Liu C. Increased expression of lncRNA FTH1P3 promotes oral squamous cell carcinoma cells migration and invasion by enhancing PI3K/Akt/GSK3b/Wnt/beta-catenin signaling. Eur Rev Med Pharmacol Sci. 2018;22(23):8306–14.PubMed
100.
Chi H. miR-194 regulated AGK and inhibited cell proliferation of oral squamous cell carcinoma by reducing PI3K-Akt-FoxO3a signaling. Biomed Pharmacother. 2015;71:53–7.PubMedCrossRef
101.
Ferreira DM, Neves TJ, Lima LGC, Alves FA, Begnami MD. Prognostic implications of the phosphatidylinositol 3-kinase/Akt signaling pathway in oral squamous cell carcinoma: overexpression of p-mTOR indicates an adverse prognosis. Appl Cancer Res. 2017;37(1):1–8.CrossRef
102.
Gao P, Li C, Chang Z, Wang X, Xuan M. Carcinoma associated fibroblasts derived from oral squamous cell carcinoma promote lymphangiogenesis via c-Met/PI3K/AKT in vitro. Oncol Lett. 2018;15(1):331–7.PubMed
103.
Gu Y, Liu H, Kong F, Ye J, Jia X, Zhang Z, et al. miR-22/KAT6B axis is a chemotherapeutic determiner via regulation of PI3k-Akt-NF-kB pathway in tongue squamous cell carcinoma. J Exp Clin Cancer Res. 2018;37(1):1–14.CrossRef
104.
Lee TK, Park C, Jeong SJ, Jeong MJ, Kim GY, Kim WJ, et al. Sanguinarine induces apoptosis of human oral squamous cell carcinoma KB cells via inactivation of the PI3K/Akt signaling pathway. Drug Dev Res. 2016;77(5):227–40.PubMedCrossRef
105.
Matsuo FS, Andrade MF, Loyola AM, da Silva SJ, Silva MJB, Cardoso SV, et al. Pathologic significance of AKT, mTOR, and GSK3β proteins in oral squamous cell carcinoma-affected patients. Virchows Arch. 2018;472(6):983–97.PubMedCrossRef
106.
Smolensky D, Rathore K, Bourn J, Cekanova M. Inhibition of the PI3K/AKT pathway sensitizes oral squamous cell carcinoma cells to anthracycline-based chemotherapy in vitro. J Cell Biochem. 2017;118(9):2615–24.PubMedPubMedCentralCrossRef
107.
Yu C-C, Hung S-K, Lin H-Y, Chiou W-Y, Lee M-S, Liao H-F, et al. Targeting the PI3K/AKT/mTOR signaling pathway as an effectively radiosensitizing strategy for treating human oral squamous cell carcinoma in vitro and in vivo. Oncotarget. 2017;8(40):68641.PubMedPubMedCentralCrossRef
108.
Wang H, Deng X, Zhang J, Ou Z, Mai J, Ding S, et al. Elevated expression of zinc finger protein 703 promotes cell proliferation and metastasis through PI3K/AKT/GSK-3β signalling in oral squamous cell carcinoma. Cell Physiol Biochem. 2017;44(3):920–34.PubMedCrossRef
109.
Wang Q, Zhang X, Song X, Zhang L. Overexpression of T-cadherin inhibits the proliferation of oral squamous cell carcinoma through the PI3K/AKT/mTOR intracellular signalling pathway. Arch Oral Biol. 2018;96:74–9.PubMedCrossRef
110.
Wei J, Wu J, Xu W, Nie H, Zhou R, Wang R, et al. Salvianolic acid B inhibits glycolysis in oral squamous cell carcinoma via targeting PI3K/AKT/HIF-1α signaling pathway. Cell Death Dis. 2018;9(6):1–16.CrossRef
111.
Yang H, Wen L, Wen M, Liu T, Zhao L, Wu B, et al. FoxM1 promotes epithelial–mesenchymal transition, invasion, and migration of tongue squamous cell carcinoma cells through a c-Met/AKT-dependent positive feedback loop. Anticancer Drugs. 2018;29(3):216.PubMedPubMedCentralCrossRef
112.
Yang J, Ren X, Zhang L, Li Y, Cheng B, Xia J. Oridonin inhibits oral cancer growth and PI3K/Akt signaling pathway. Biomed Pharmacother. 2018;100:226–32.PubMedCrossRef
113.
Pan S-T, Qin Y, Zhou Z-W, He Z-X, Zhang X, Yang T, et al. Plumbagin induces G2/M arrest, apoptosis, and autophagy via p38 MAPK-and PI3K/Akt/mTOR-mediated pathways in human tongue squamous cell carcinoma cells. Drug Des Dev Ther. 2015;9:1601.
114.
Zhu L, Shen Y, Sun W. Paraoxonase 3 promotes cell proliferation and metastasis by PI3K/Akt in oral squamous cell carcinoma. Biomed Pharmacother. 2017;85:712–7.PubMedCrossRef
115.
Wang F, Ma H, Liu Z, Huang W, Xu X, Zhang X. α-Mangostin inhibits DMBA/TPA-induced skin cancer through inhibiting inflammation and promoting autophagy and apoptosis by regulating PI3K/Akt/mTOR signaling pathway in mice. Biomed Pharmacother. 2017;92:672–80.PubMedCrossRef
116.
Yao M, Shang Y-Y, Zhou Z-W, Yang Y-X, Wu Y-S, Guan L-F, et al. The research on lapatinib in autophagy, cell cycle arrest and epithelial to mesenchymal transition via Wnt/ErK/PI3K-AKT signaling pathway in human cutaneous squamous cell carcinoma. J Cancer. 2017;8(2):220.PubMedPubMedCentralCrossRef
117.
Fu J, Zhao J, Zhang H, Fan X, Geng W, Qiao S. MicroRNA-451a prevents cutaneous squamous cell carcinoma progression via the 3-phosphoinositide-dependent protein kinase-1-mediated PI3K/AKT signaling pathway. Exp Therapeutic Med. 2021;21(2):1.
118.
Mei X-L, Zhong S. Long noncoding RNA LINC00520 prevents the progression of cutaneous squamous cell carcinoma through the inactivation of the PI3K/Akt signaling pathway by downregulating EGFR. Chin Med J. 2019;132(4):454.PubMedPubMedCentralCrossRef
119.
Zeng N, Hongbo T, Xu Y, Wu M, Wu Y. Anticancer activity of caffeic acid n-butyl ester against A431 skin carcinoma cell line occurs via induction of apoptosis and inhibition of the mTOR/PI3K/AKT signaling pathway. Mol Med Rep. 2018;17(4):5652–7.PubMedPubMedCentral
120.
Ci C, Wu C, Lyu D, Chang X, He C, Liu W, et al. Downregulation of kynureninase restrains cutaneous squamous cell carcinoma proliferation and represses the PI3K/AKT pathway. Clin Exp Dermatol. 2020;45(2):194–201.PubMedCrossRef
121.
Sun Y, Tu Y, He L, Ji C, Cheng B. High mobility group box 1 regulates tumor metastasis in cutaneous squamous cell carcinoma via the PI3K/AKT and MAPK signaling pathways. Oncol Lett. 2016;11(1):59–62.PubMedCrossRef
122.
Marques AEM, Borges GA, Viesi CH, Vianna LMS, Ramos D, Castilho RM, et al. Expression profile of the PI3K-AKT-mTOR pathway in head and neck squamous cell carcinoma: data from Brazilian population. Oral Surg Oral Med Oral Pathol Oral Radiol. 2022;133(4):453–61.PubMedCrossRef
123.
Ghafouri-Fard S, Abak A, Tondro Anamag F, Shoorei H, Majidpoor J, Taheri M. The emerging role of non-coding RNAs in the regulation of PI3K/AKT pathway in the carcinogenesis process. Biomed pharmacother. 2021;137:111279.PubMedCrossRef
Metadata
Title
Role of PI3K/AKT pathway in squamous cell carcinoma with an especial focus on head and neck cancers
Authors
Soudeh Ghafouri-Fard
Ali Noie Alamdari
Yashar Noee Alamdari
Atefe Abak
Bashdar Mahmud Hussen
Mohammad Taheri
Elena Jamali
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-022-02676-x

Other articles of this Issue 1/2022

Cancer Cell International 1/2022 Go to the issue

Research

Clinical usefulness and acceleratory effect of macrophage inhibitory cytokine-1 on biliary tract cancer: an experimental biomarker analysis

Primary research

SNAP25 is a potential prognostic biomarker for prostate cancer

Review

The emerging role of deubiquitylating enzymes as therapeutic targets in cancer metabolism

Review

From inflammatory bowel disease to colorectal cancer: what’s the role of miRNAs?

Research

Crosstalk between tumor-associated macrophages and tumor cells promotes chemoresistance via CXCL5/PI3K/AKT/mTOR pathway in gastric cancer

Research

Combinatorial targeting of menin and the histone methyltransferase DOT1L as a novel therapeutic strategy for treatment of chemotherapy-resistant ovarian cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits