The Role of PI3K/AKT Signaling Pathway in Gallbladder Carcinoma

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2022 Aug 12

PMID 35958463

Authors

Zeyu Wu

Xiao Yu

Shuijun Zhang

Yuting He

Wenzhi Guo

Affiliations

Soon will be listed here.

Abstract

Objectives: The prognosis of gallbladder carcinoma (GBC) is poor, with a less than 5% five-year survival rate. Identifying the mechanisms underlying GBC occurrence and advancement is necessary to improve GBC patient prognosis and survival rates. The phosphatidylinositol 3-kinase (PI3K)/serine-threonine kinase (AKT) pathway is involved in cancer deterioration, tumor growth, cell proliferation, and distant metastasis. Studying the impacts of the PI3K/AKT pathway has resulted in the identification of key factors involved in GBC progression that might serve as therapeutic targets, promoting the development of new treatments.

Methods: We reviewed recent literature exploring abnormal regulation of the PI3K/AKT pathway in gallbladder cancer, with a focus on abnormal RNA levels, protein level regulation, and drug treatment advances.

Results: Further investigation of the regulation of small molecules and proteins by the PI3K/AKT pathway might ultimately provide new diagnostic or prognostic markers or cancer treatment targets. Recent studies have focused on RNA and proteins involved in the regulation of the cell cycle or cell movement in cancer progression via PI3K/AKT pathway, the use of anticancer drug combinations, or the anticancer effects of drugs not currently utilized for cancer treatment.

Conclusions: We herein review the known available molecules that affect the PI3K/AKT pathway in patients with GBC and the mechanisms of drug action associated with this pathway.

Citing Articles

Bioinformatics analysis reveals 's prognostic significance in head and neck squamous cell carcinoma and its association with immune cell infiltration.

Tang Y, Hu T, Yin W, Huang C, Liu D, Lai F Transl Cancer Res. 2024; 13(11):5953-5970.

PMID: 39697755 PMC: 11651743. DOI: 10.21037/tcr-24-834.

Unraveling the role of LncRNAs in glioblastoma progression: insights into signaling pathways and therapeutic potential.

Doghish A, Abd-Elmawla M, Hatawsh A, Zaki M, Aborehab N, Radwan A Metab Brain Dis. 2024; 40(1):42.

PMID: 39589598 DOI: 10.1007/s11011-024-01456-y.

Research Progress of Chinese Medicine Monomers in Treatment of Cholangiocarcinoma.

Wang X, Wang X, Luo K, Bai H, Qi J, Zhang G Chin J Integr Med. 2024; 31(2):170-182.

PMID: 39470920 DOI: 10.1007/s11655-024-4203-9.

Molecular biomarkers involved in the progression of gallbladder inflammatory lesions to invasive cancer: A proteomic approach.

Rawal N, Hariprasad G, Bandyopadhyay S, Dash N, Kumar S, Das P Biomol Biomed. 2024; 25(1):115-143.

PMID: 39284282 PMC: 11647257. DOI: 10.17305/bb.2024.10704.

First total synthesis, antitumor evaluation and target identification of mornaphthoate E: A new tubulin inhibitor template acting on PI3K/Akt signaling pathway.

Shan P, Ye T, Tang Y, Song H, Wang C, Zhu K Acta Pharm Sin B. 2024; 14(5):2177-2193.

PMID: 38799630 PMC: 11120283. DOI: 10.1016/j.apsb.2024.02.012.

References

Lv T, Yang C, Regmi P, Ma W, Hu H, Liu F . The role of laparoscopic surgery in the surgical management of gallbladder carcinoma: A systematic review and meta-analysis. Asian J Surg. 2021; 44(12):1493-1502. DOI: 10.1016/j.asjsur.2021.03.015. View

Ye J, Qi L, Liang J, Zong K, Liu W, Li R . Lenvatinib induces anticancer activity in gallbladder cancer by targeting AKT. J Cancer. 2021; 12(12):3548-3557. PMC: 8120192. DOI: 10.7150/jca.50292. View

Kim S, Ha S, Lee H, Rampogu S, Vetrivel P, Kim H . Sinensetin Induces Autophagic Cell Death through p53-Related AMPK/mTOR Signaling in Hepatocellular Carcinoma HepG2 Cells. Nutrients. 2020; 12(8). PMC: 7468969. DOI: 10.3390/nu12082462. View

Ruan X, Liu X, Yang Z, Zhang S, Li Q, Lin C . INPP4B promotes colorectal cancer cell proliferation by activating mTORC1 signaling and cap-dependent translation. Onco Targets Ther. 2019; 12:3109-3117. PMC: 6485035. DOI: 10.2147/OTT.S186365. View

Zhai T, Zhang X, Hei Z, Jin L, Han C, Ko A . Isorhamnetin Inhibits Human Gallbladder Cancer Cell Proliferation and Metastasis via PI3K/AKT Signaling Pathway Inactivation. Front Pharmacol. 2021; 12:628621. PMC: 7927673. DOI: 10.3389/fphar.2021.628621. View

Li Y, Li S, Lin C . Effect of resveratrol and pterostilbene on aging and longevity. Biofactors. 2017; 44(1):69-82. DOI: 10.1002/biof.1400. View

Hamila S, Ooms L, Rodgers S, Mitchell C . The INPP4B paradox: Like PTEN, but different. Adv Biol Regul. 2021; 82:100817. DOI: 10.1016/j.jbior.2021.100817. View

Qian L, Su H, Wang G, Li B, Shen G, Gao Q . Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer. J Cancer. 2020; 11(11):3114-3123. PMC: 7097950. DOI: 10.7150/jca.38393. View

Cai Q, Wang Z, Wang S, Li C, Zhu Z, Quan Z . Upregulation of long non-coding RNA LINC00152 by SP1 contributes to gallbladder cancer cell growth and tumor metastasis via PI3K/AKT pathway. Am J Transl Res. 2016; 8(10):4068-4081. PMC: 5095302. View

10.

Sheng S, Jiwen W, Dexiang Z, Bohao Z, Yueqi W, Han L . DMBT1 suppresses progression of gallbladder carcinoma through PI3K/AKT signaling pathway by targeting PTEN. Biosci Biotechnol Biochem. 2019; 83(12):2257-2264. DOI: 10.1080/09168451.2019.1654361. View

11.

Xuan L, Zhang J, Ji J, Hu J, Li F . Oroxylin A Exerts Its Antitumor Effects in Human Gallbladder Cancer via Inhibition of the PTEN/PI3K/AKT Signaling Pathway. Biol Pharm Bull. 2020; 43(10):1511-1518. DOI: 10.1248/bpb.b20-00262. View

12.

Hu Y, Wu Z, Jiang L, Jin Y, Li H, Zhang Y . STYK1 promotes cancer cell proliferation and malignant transformation by activating PI3K-AKT pathway in gallbladder carcinoma. Int J Biochem Cell Biol. 2018; 97:16-27. DOI: 10.1016/j.biocel.2018.01.016. View

13.

Ye Z, Chen J, Hu X, Yang S, Xuan Z, Lu X . SPOCK1: a multi-domain proteoglycan at the crossroads of extracellular matrix remodeling and cancer development. Am J Cancer Res. 2020; 10(10):3127-3137. PMC: 7642659. View

14.

Obrador E, Salvador-Palmer R, Jihad-Jebbar A, Lopez-Blanch R, Dellinger T, Dellinger R . Pterostilbene in Cancer Therapy. Antioxidants (Basel). 2021; 10(3). PMC: 8004113. DOI: 10.3390/antiox10030492. View

15.

Su L, Zhang J, Zhang X, Zheng L, Zhu Z . Identification of cell cycle as the critical pathway modulated by exosome-derived microRNAs in gallbladder carcinoma. Med Oncol. 2021; 38(12):141. PMC: 8520510. DOI: 10.1007/s12032-021-01594-8. View

16.

Le T, Pulat S, Lee J, Kim G, Kim H, Lee E . Marine Depsipeptide Nobilamide I Inhibits Cancer Cell Motility and Tumorigenicity via Suppressing Epithelial-Mesenchymal Transition and MMP2/9 Expression. ACS Omega. 2022; 7(2):1722-1732. PMC: 8771697. DOI: 10.1021/acsomega.1c04520. View

17.

Chen L, Yuan R, Wen C, Liu T, Feng Q, Deng X . E3 ubiquitin ligase UBR5 promotes pancreatic cancer growth and aerobic glycolysis by downregulating FBP1 via destabilization of C/EBPα. Oncogene. 2020; 40(2):262-276. DOI: 10.1038/s41388-020-01527-1. View

18.

Teng Y, Fan Y, Ma J, Lu W, Liu N, Chen Y . The PI3K/Akt Pathway: Emerging Roles in Skin Homeostasis and a Group of Non-Malignant Skin Disorders. Cells. 2021; 10(5). PMC: 8156939. DOI: 10.3390/cells10051219. View

19.

Chen Q, Wu K, Qin X, Yu Y, Wang X, Wei K . LASP1 promotes proliferation, metastasis, invasion in head and neck squamous cell carcinoma and through direct interaction with HSPA1A. J Cell Mol Med. 2019; 24(2):1626-1639. PMC: 6991697. DOI: 10.1111/jcmm.14854. View

20.

Kopustinskiene D, Jakstas V, Savickas A, Bernatoniene J . Flavonoids as Anticancer Agents. Nutrients. 2020; 12(2). PMC: 7071196. DOI: 10.3390/nu12020457. View