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On-line Access: 2024-07-17

Received: 2023-06-26

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Wen XIE

0009-0003-9093-9627

Jie LIU

0009-0000-3807-226X

Caiping REN

0000-0001-6880-7394

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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.7 P.541-556

http://doi.org/10.1631/jzus.B2300457


Roles of THEM4 in the Akt pathway: a double-edged sword


Author(s):  Wen XIE, Weidong LIU, Lei WANG, Bin ZHU, Cong ZHAO, Ziling LIAO, Yihan LI, Xingjun JIANG, Jie LIU, Caiping REN

Affiliation(s):  NHC Key Laboratory of Carcinogenesis, Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China; more

Corresponding email(s):   rencaiping@csu.edu.cn, braindream@163.com

Key Words:  Protein kinase B (Akt), Thioesterase superfamily member 4 (THEM4), Tumor proliferation, Tumor metastasis


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Wen XIE, Weidong LIU, Lei WANG, Bin ZHU, Cong ZHAO, Ziling LIAO, Yihan LI, Xingjun JIANG, Jie LIU, Caiping REN. Roles of THEM4 in the Akt pathway: a double-edged sword[J]. Journal of Zhejiang University Science B, 2024, 25(7): 541-556.

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journal="Journal of Zhejiang University Science B",
volume="25",
number="7",
pages="541-556",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300457"
}

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%A Ziling LIAO
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%A Xingjun JIANG
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A1 - Cong ZHAO
A1 - Ziling LIAO
A1 - Yihan LI
A1 - Xingjun JIANG
A1 - Jie LIU
A1 - Caiping REN
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Abstract: 
The protein kinase B (Akt) pathway can regulate the growth, proliferation, and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes, thus affecting the development and treatment of a range of diseases. thioesterase superfamily member 4 (THEM4), a member of the thioesterase superfamily, is one of the Akt kinase-binding proteins. Some studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its phosphorylation. Initially, THEM4 was considered an endogenous inhibitor of Akt, which can inhibit the phosphorylation of Akt in diseases such as lung cancer, pancreatic cancer, and liver cancer, but subsequently, THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma, which contradicts previous findings. Considering these two distinct views, this review summarizes the important roles of THEM4 in the Akt pathway, focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases, especially cancer. This work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

THEM4在Akt通路中的作用:一把双刃剑

谢雯1,2,3,刘卫东1,2,3,王磊1,2,3,祝斌1,2,3,赵聪1,2,3,廖紫凌1,2,3,李一韩1,2,3,蒋星军1,刘杰4,任彩萍1,2,3
1中南大学湘雅医院神经外科,国家卫生健康委肿瘤发生重点实验室,中国长沙市,410008
2中南大学湘雅医院国家老年疾病临床研究中心,中国长沙市,410008
3中南大学基础医学院肿瘤研究所,肿瘤发生与侵袭教育部重点实验室,中国长沙市,410078
4中国人民解放军总医院海南医院重症医学科,中国三亚市,572013
摘要:蛋白激酶B(Akt)通路可通过激活下游多个靶基因来调控肿瘤细胞和干细胞的生长、增殖和代谢等,从而影响一系列疾病的发生和治疗。硫酯酶超家族成员4(THEM4)作为硫酯酶超家族成员中的一员,也是Akt激酶的结合蛋白之一。癌症等疾病的机制研究发现THEM4可以与Akt结合从而调控Akt的磷酸化。最初,THEM4被认为是Akt的内源性抑制剂,在肺癌、胰腺癌和肝癌等疾病中抑制Akt的磷酸化。但随后的研究发现,THEM4在乳腺癌和鼻咽癌中通过正向调节Akt活性促进肿瘤细胞的增殖,这与之前的研究结果正好相反。面对这两种截然不同的观点,本文综述了THEM4在Akt通路中的重要作用,重点探讨了THEM4作为一种Akt结合蛋白,在各种疾病(尤其是癌症)中与Akt磷酸化的调控关系。这将有助于更好地了解THEM4联合Akt在疾病治疗中的作用。

关键词:蛋白激酶B(Akt);硫酯酶超家族成员4(THEM4);肿瘤增殖;肿瘤转移

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AbeyrathnaP, SuYC, 2015. The critical role of Akt in cardiovascular function. Vascul Pharmacol, 74:38-48.

[2]AngellottiE, D'AlessioD, Dawson-HughesB, et al., 2019. Effect of vitamin D supplementation on cardiovascular risk in type 2 diabetes. Clin Nutr, 38(5):2449-2453.

[3]AnwanwanD, SinghSK, SinghS, et al., 2020. Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta (BBA) Rev Cancer, 1873(1):188314.

[4]AustinS, NowikovskyK, 2019. LETM1: essential for mitochondrial biology and cation homeostasis? Trends Biochem Sci, 44(8):648-658.

[5]CaswellBT, de CarvalhoCC, NguyenH, et al., 2022. Thioesterase enzyme families: functions, structures, and mechanisms. Protein Sci, 31(3):652-676.

[6]ChangJW, JungSN, KimJH, et al., 2016. Carboxyl-terminal modulator protein positively acts as an oncogenic driver in head and neck squamous cell carcinoma via regulating Akt phosphorylation. Sci Rep, 6:28503.

[7]CheN, YangZT, LiuXZ, et al., 2021. Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species-induced autophagy. J Cell Mol Med, 25(4):2110-2120.

[8]ChenN, HaoJ, LiLS, et al., 2016. Carboxy-terminal modulator protein attenuated extracellular matrix deposit by inhibiting phospho-Akt, TGF-β1 and α-SMA in kidneys of diabetic mice. Biochem Biophys Res Commun, 474(4):753-760.

[9]ChenYC, LiHY, LiangJL, et al., 2017. CTMP, a predictive biomarker for trastuzumab resistance in HER2-enriched breast cancer patient. Oncotarget, 8(18):29699-29710.

[10]CollissonEA, BaileyP, ChangDK, et al., 2019. Molecular subtypes of pancreatic cancer. Nat Rev Gastroenterol Hepatol, 16(4):207-220.

[11]de LimaJGS, LanzaDCF, 2021. 2A and 2A-like sequences: distribution in different virus species and applications in biotechnology. Viruses, 13(11):2160.

[12]DumaN, Santana-DavilaR, MolinaJR, 2019. Non-small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc, 94(8):1623-1640.

[13]FallatahB, ShuaibM, AdroubS, et al., 2021. Ago1 controls myogenic differentiation by regulating eRNA-mediated CBP-guided epigenome reprogramming. Cell Rep, 37(9):110066.

[14]GiustinaA, AdlerRA, BinkleyN, et al., 2020. Consensus statement from 2nd international conference on controversies in vitamin D. Rev Endocr Metab Disord, 21(1):89-116.

[15]GravitzL, 2014. Liver cancer. Nature, 516(7529):S1.

[16]GurneyME, PuHF, ChiuAY, et al., 1994. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science, 264(5166):1772-1775.

[17]HassounPM, 2021. Pulmonary arterial hypertension. N Engl J Med, 385(25):2361-2376.

[18]HsiehTC, LinCY, BennettDJ, et al., 2014. Biochemical and cellular evidence demonstrating AKT-1 as a binding partner for resveratrol targeting protein NQO2. PLoS ONE, 9(6):e101070.

[19]HuangCY, ChenJJ, WuJS, et al., 2015. Novel link of anti-apoptotic ATF3 with pro-apoptotic CTMP in the ischemic brain. Mol Neurobiol, 51(2):543-557.

[20]HuangSH, O'SullivanB, 2017. Overview of the 8th edition TNM classification for head and neck cancer. Curr Treat Options Oncol, 18(7):40.

[21]HwangSK, KwonJT, ParkSJ, et al., 2007. Lentivirus-mediated carboxyl-terminal modulator protein gene transfection via aerosol in lungs of K-ras null mice. Gene Ther, 14(24):1721-1730.

[22]HwangSK, LimHT, Minai-TehraniA, et al., 2009. Repeated aerosol delivery of carboxyl-terminal modulator protein suppresses tumor in the lungs of K-rasLA1 mice. Am J Respir Crit Care Med, 179(12):1131-1140.

[23]JafariM, GhadamiE, DadkhahT, et al., 2019. PI3K/Akt signaling pathway: erythropoiesis and beyond. J Cell Physiol, 234(3):2373-2385.

[24]JagannathVA, FilippiniG, do NascimentoIJB, et al., 2018. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev, 9(9):CD008422.

[25]JeongD, HamJ, KimHW, et al., 2021. ELOVL2: a novel tumor suppressor attenuating tamoxifen resistance in breast cancer. Am J Cancer Res, 11(6):2568-2589.

[26]JinH, XuCX, LimHT, et al., 2009. High dietary inorganic phosphate increases lung tumorigenesis and alters Akt signaling. Am J Respir Crit Care Med, 179(1):59-68.

[27]KaoMH, HuangCY, CheungWM, et al., 2023. Activating transcription factor 3 diminishes ischemic cerebral infarct and behavioral deficit by downregulating carboxyl-terminal modulator protein. Int J Mol Sci, 24(3):2306.

[28]KleinAP, 2021. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat Rev Gastroenterol Hepatol, 18(7):493-502.

[29]LiJ, ShanWR, ZuoZY, 2018. Age-related upregulation of carboxyl terminal modulator protein contributes to the decreased brain ischemic tolerance in older rats. Mol Neurobiol, 55(7):6145-6154.

[30]LiL, FanCM, 2017. A CREB-MPP7-AMOT regulatory axis controls muscle stem cell expansion and self-renewal competence. Cell Rep, 21(5):1253-1266.

[31]LiY, ImaiN, NichollsHT, et al., 2021. Thioesterase superfamily member 1 undergoes stimulus-coupled conformational reorganization to regulate metabolism in mice. Nat Commun, 12:3493.

[32]LiY, SheWY, XuXR, et al., 2023. AAZ2 induces mitochondrial-dependent apoptosis by targeting PDK1 in gastric cancer. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 24(3):232-247.

[33]LiZH, CaiBL, AbdallaBA, et al., 2019. LncIRS1 controls muscle atrophy via sponging miR-15 family to activate IGF1-PI3K/AKT pathway. J Cachexia Sarcopenia Muscle, 10(2):391-410.

[34]LinCH, LinWD, HuangYC, et al., 2023. Carboxyl-terminal modulator protein facilitates tumor metastasis in triple-negative breast cancer. Cancer Gene Ther, 30(3):404-413.

[35]LiuXX, YangQ, ZhuLH, et al., 2018. Carboxyl-terminal modulator protein ameliorates pathological cardiac hypertrophy by suppressing the protein kinase B signaling pathway. J Am Heart Assoc, 7(13):e008654.

[36]LiuYP, LiaoWC, GerLP, et al., 2013. Carboxyl-terminal modulator protein positively regulates Akt phosphorylation and acts as an oncogenic driver in breast cancer. Cancer Res, 73(20):6194-6205.

[37]MaZ, LouSP, JiangZ, 2020. PHLDA2 regulates EMT and autophagy in colorectal cancer via the PI3K/AKT signaling pathway. Aging (Albany NY), 12(9):7985-8000.

[38]MaieseK, ChongZZ, WangSH, et al., 2012. Oxidant stress and signal transduction in the nervous system with the PI 3-K, Akt, and mTOR cascade. Int J Mol Sci, 13(11):13830-13866.

[39]MairaSM, GaleticI, BrazilDP, et al., 2001. Carboxyl-terminal modulator protein (CTMP), a negative regulator of PKB/Akt and v-Akt at the plasma membrane. Science, 294(5541):374-380.

[40]MasroriP, van DammeP, 2020. Amyotrophic lateral sclerosis: a clinical review. Eur J Neurol, 27(10):1918-1929.

[41]MejziniR, FlynnLL, PitoutIL, et al., 2019. ALS genetics, mechanisms, and therapeutics: where are we now? Front Neurosci, 13:1310.

[42]MissiroliS, PerroneM, GenoveseI, et al., 2020. Cancer metabolism and mitochondria: finding novel mechanisms to fight tumours. EBioMedicine, 59:102943.

[43]MiyawakiT, OfengeimD, NohKM, et al., 2009. The endogenous inhibitor of Akt, CTMP, is critical to ischemia-induced neuronal death. Nat Neurosci, 12(5):618-626.

[44]NarayanankuttyA, 2019. PI3K/Akt/mTOR pathway as a thera-peutic target for colorectal cancer: a review of preclinical and clinical evidence. Curr Drug Targets, 20(12):1217-1226.

[45]NatarajanGK, MishraJ, CamaraAKS, et al., 2021. LETM1: a single entity with diverse impact on mitochondrial metabolism and cellular signaling. Front Physiol, 12:637852.

[46]NiFB, LinZ, FanXH, et al., 2020. A novel genomic-clinicopathologic nomogram to improve prognosis prediction of hepatocellular carcinoma. Clin Chim Acta, 504:88-97.

[47]OnoH, SakodaH, FujishiroM, et al., 2007. Carboxy-terminal modulator protein induces Akt phosphorylation and activation, thereby enhancing antiapoptotic, glycogen synthetic, and glucose uptake pathways. Am J Physiol Cell Physiol, 293(5):C1576-C1585.

[48]ParkJ, LiYW, KimSH, et al., 2014. New players in high fat diet-induced obesity: LETM1 and CTMP. Metabolism, 63(3):318-327.

[49]PiaoL, YangZT, FengY, et al., 2019a. LETM1 is a potential biomarker of prognosis in lung non-small cell carcinoma. BMC Cancer, 19:898.

[50]PiaoL, FengY, YangZT, et al., 2019b. LETM1 is a potential cancer stem-like cell marker and predicts poor prognosis in colorectal adenocarcinoma. Pathol Res Pract, 215(7):152437.

[51]PorporatoPE, FilighedduN, PedroJMBS, et al., 2018. Mitochondrial metabolism and cancer. Cell Res, 28(3):265-280.

[52]RevathideviS, MunirajanAK, 2019. Akt in cancer: mediator and more. Semin Cancer Biol, 59:80-91.

[53]SarbassovDD, GuertinDA, AliSM, et al., 2005. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science, 307(5712):1098-1101.

[54]ShariatiM, Meric-BernstamF, 2019. Targeting AKT for cancer therapy. Expert Opin Investig Drugs, 28(11):977-988.

[55]ShinJY, ChungYS, KangB, et al., 2013. Co-delivery of LETM1 and CTMP synergistically inhibits tumor growth in H-ras12V liver cancer model mice. Cancer Gene Ther, 20(3):186-194.

[56]ShinN, YiMH, KimS, et al., 2017. Astrocytic expression of CTMP following an excitotoxic lesion in the mouse hippocampus. Exp Neurobiol, 26(1):25-32.

[57]SimonPO, McDunnJE, KashiwagiH, et al., 2009. Targeting AKT with the proapoptotic peptide, TAT-CTMP: a novel strategy for the treatment of human pancreatic adenocarcinoma. Int J Cancer, 125(4):942-951.

[58]SongMQ, BodeAM, DongZG, et al., 2019. AKT as a therapeutic target for cancer. Cancer Res, 79(6):1019-1031.

[59]SumiT, TsuneyoshiN, NakatsujiN, et al., 2008. Defining early lineage specification of human embryonic stem cells by the orchestrated balance of canonical Wnt/β-catenin, Activin/Nodal and BMP signaling. Development, 135(17):2969-2979.

[60]SunXT, KellnerM, DesaiAA, et al., 2016. Asymmetric dimethylarginine stimulates Akt1 phosphorylation via heat shock protein 70-facilitated carboxyl-terminal modulator protein degradation in pulmonary arterial endothelial cells. Am J Respir Cell Mol Biol, 55(2):275-287.

[61]SuoCJ, GuiZP, WangZJ, et al., 2021. Bortezomib limits renal allograft interstitial fibrosis by inhibiting NF-κB/TNF-α/Akt/mTOR/P70S6K/Smurf2 pathway via IκBα protein stabilization. Clin Sci (Lond), 135(1):53-69.

[62]ThaiAA, SolomonBJ, SequistLV, et al., 2021. Lung cancer. Lancet, 398(10299):535-554.

[63]TillanderV, MiniamiA, Alves-BezerraM, et al., 2019. Thioesterase superfamily member 2 promotes hepatic insulin resistance in the setting of glycerol-3-phosphate acyltransferase 1-induced steatosis. J Biol Chem, 294(6):2009-2020.

[64]TrayesKP, CokenakesSEH, 2021. Breast cancer treatment. Am Fam Physician, 104(2):171-178.

[65]VaesN, SchonkerenSL, RademakersG, et al., 2021. Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2. EMBO Rep, 22(6):e51913.

[66]VincentA, HermanJ, SchulickR, et al., 2011. Pancreatic cancer. Lancet, 378(9791):607-620.

[67]WangB, XuX, LiuX, et al., 2021. Enolase-phosphatase 1 acts as an oncogenic driver in glioma. J Cell Physiol, 236(2):1184-1194.

[68]WangDT, YinY, YangYJ, et al., 2014. Resveratrol prevents TNF-α-induced muscle atrophy via regulation of Akt/mTOR/FoxO1 signaling in C2C12 myotubes. Int Immunopharmacol, 19(2):206-213.

[69]WangJM, FryCME, WalkerCL, 2019. Carboxyl-terminal modulator protein regulates Akt signaling during skeletal muscle atrophy in vitro and a mouse model of amyotrophic lateral sclerosis. Sci Rep, 9:3920.

[70]WangJM, TierneyL, WilsonC, et al., 2023. Carboxyl-terminal modulator protein (CTMP) deficiency mitigates denervation-induced skeletal muscle atrophy. Biochem Biophys Res Commun, 644:155-161.

[71]WangQS, HeYH, ShenYJ, et al., 2014. Vitamin D inhibits COX-2 expression and inflammatory response by targeting thioesterase superfamily member 4. J Biol Chem, 289(17):11681-11694.

[72]WangWY, WenQY, XuLN, et al., 2014. Activation of Akt/mTOR pathway is associated with poor prognosis of nasopharyngeal carcinoma. PLoS ONE, 9(8):e106098.

[73]WangXK, MarchisioMA, 2021. Synthetic polycistronic sequences in eukaryotes. Synth Syst Biotechnol, 6(4):254-261.

[74]WenL, LiuL, TongLY, et al., 2019. NDRG4 prevents cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis. Genes Dis, 6(4):448-454.

[75]WuX, LiangYR, JingXN, et al., 2018. Rifampicin prevents SH-SY5Y cells from rotenone-induced apoptosis via the PI3K/Akt/GSK-3β/CREB signaling pathway. Neurochem Res, 43(4):886-893.

[76]XuHJ, YanXJ, ZhuHC, et al., 2022. TBL1X and Flot2 form a positive feedback loop to promote metastasis in nasopharyngeal carcinoma. Int J Biol Sci, 18(3):1134-1149.

[77]YinHD, HeHR, ShenXX, et al., 2020. MiR-9-5p inhibits skeletal muscle satellite cell proliferation and differentiation by targeting IGF2BP3 through the IGF2-PI3K/Akt signaling pathway. Int J Mol Sci, 21(5):1655.

[78]ZengJ, HeSL, LiLJ, et al., 2021. Hsp90 up-regulates PD-L1 to promote HPV-positive cervical cancer via HER2/PI3K/AKT pathway. Mol Med, 27:130.

[79]ZhangEY, ShiHL, YangL, et al., 2017. Ginsenoside Rd regulates the Akt/mTOR/p70S6K signaling cascade and suppresses angiogenesis and breast tumor growth. Oncol Rep, 38(1):359-367.

[80]ZhangSS, XueR, GengYP, et al., 2020. Fisetin prevents HT22 cells from high glucose-induced neurotoxicity via PI3K/Akt/CREB signaling pathway. Front Neurosci, 14:241.

[81]ZhangSX, LiDG, ZhaoM, et al., 2021. Exosomal miR-183-5p shuttled by M2 polarized tumor-associated macrophage promotes the development of colon cancer via targeting THEM4 mediated PI3K/AKT and NF-κB pathways. Front Oncol, 11:672684.

[82]ZhangX, DongZC, FanH, et al., 2023. Scutellarin prevents acute alcohol-induced liver injury via inhibiting oxidative stress by regulating the Nrf2/HO-1 pathway and inhibiting inflammation by regulating the AKT, p38 MAPK/NF-κB pathways. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 24(7):617-631.

[83]ZhaoH, LimK, ChoudryA, et al., 2012. Correlation of structure and function in the human hotdog-fold enzyme hTHEM4. Biochemistry, 51(33):6490-6492.

[84]ZhaoSJ, KongFQ, JieJ, et al., 2020. Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K/AKT/GSK3β/β-catenin pathway. Theranostics, 10(1):17-35.

[85]ZhouBY, YangCH, YanX, et al., 2020. LETM1 knockdown promotes autophagy and apoptosis through AMP-activated protein kinase phosphorylation-mediated Beclin-1/Bcl-2 complex dissociation in hepatocellular carcinoma. Front Oncol, 10:606790.

[86]ZhuMF, ZhengR, GuoYW, et al., 2017. NDRG4 promotes myogenesis via Akt/CREB activation. Oncotarget, 8(60):101720-101734.

[87]ZhuravlevaE, GutH, HynxD, et al., 2012. Acyl coenzyme A thioesterase Them5/Acot15 is involved in cardiolipin remodeling and fatty liver development. Mol Cell Biol, 32(14):2685-2697.

[88]ZongWX, RabinowitzJD, WhiteE, 2016. Mitochondria and cancer. Mol Cell, 61(5):667-676.

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