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 1/2019

Open Access 01-12-2019 | Adenovirus | Primary research

RETRACTED ARTICLE: Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway

Authors: Xiaoli Zhang, Fei Li, Yeqing Cui, Shuang Liu, Haichen Sun

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

Cancer cell viability is strongly modulated by the Hippo pathway, which includes mammalian STE20-like protein kinase 1 (Mst1) and yes-associated protein (Yap). Although the roles of Mst1 and Yap in thyroid carcinoma cell death have been fully addressed, no study has determined whether differential modification of Mst1 and Yap could further suppress thyroid carcinoma progression. The aim of our study was to explore the antiapoptotic effects exerted by combined Mst1 overexpression and Yap knockdown in thyroid carcinoma MDA-T32 cells in vitro.

Methods

Mst1 adenovirus and Yap shRNA were transfected into MDA-T32 cells to overexpress Mst1 and inhibit Yap, respectively. Cell viability and death were determined via an MTT assay, a TUNEL assay and western blotting. Mitochondrial function, mitochondrial fission and pathway studies were performed via western blotting and immunofluorescence.

Results

The results of our study showed that combined Mst1 overexpression and Yap knockdown further augmented MDA-T32 cell death by mediating mitochondrial damage. In addition, cancer cell migration and proliferation were suppressed by combined Mst1 overexpression and Yap knockdown. At the molecular level, mitochondrial membrane potential, ATP production, respiratory function, and caspase-9-related apoptosis were activated by combined Mst1 overexpression and Yap knockdown. Further, we found that fatal mitochondrial fission was augmented by combined Mst1 overexpression and Yap knockdown in a manner dependent on the JNK-MIEF1 pathway. Inhibition of JNK-MIEF1 pathway activity abolished the proapoptotic effects exerted by Mst1/Yap on MDA-T32 cells.

Conclusions

Taken together, our data suggest that Mst1 activation and Yap inhibition coordinate to augment thyroid cancer cell death by controlling the JNK-MIEF1-mitochondria pathway, suggesting that differential regulation of the core Hippo pathway components is potentially a novel therapeutic tool for the treatment of thyroid cancer.
Appendix
Available only for authorised users
Literature
1.
Reddy KRK, Dasari C, Duscharla D, Supriya B, Ram NS, Surekha MV, Kumar JM, Ummanni R. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is frequently upregulated in prostate cancer, and its overexpression conveys tumor growth and angiogenesis by metabolizing asymmetric dimethylarginine (ADMA). Angiogenesis. 2018;21(1):79–94.PubMedCrossRef
2.
Kalyanaraman B, Cheng G, Hardy M, Ouari O, Lopez M, Joseph J, Zielonka J, Dwinell MB. A review of the basics of mitochondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: therapeutic targeting of tumor mitochondria with lipophilic cationic compounds. Redox Biol. 2018;14:316–27.PubMedCrossRef
3.
Tabish TA, Zhang S, Winyard PG. Developing the next generation of graphene-based platforms for cancer therapeutics: the potential role of reactive oxygen species. Redox Biol. 2018;15:34–40.PubMedCrossRef
4.
Proietti S, Catizone A, Masiello MG, Dinicola S, Fabrizi G, Minini M, Ricci G, Verna R, Reiter RJ, Cucina A, et al. Increase in motility and invasiveness of MCF7 cancer cells induced by nicotine is abolished by melatonin through inhibition of ERK phosphorylation. J Pineal Res. 2018;64(4):e12467.PubMedCrossRef
5.
Shen YQ, Guerra-Librero A, Fernandez-Gil BI, Florido J, Garcia-Lopez S, Martinez-Ruiz L, Mendivil-Perez M, Soto-Mercado V, Acuna-Castroviejo D, Ortega-Arellano H, et al. Combination of melatonin and rapamycin for head and neck cancer therapy: suppression of AKT/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation. J Pineal Res. 2018;64(3):e12461.CrossRef
6.
Fukumoto M, Kondo K, Uni K, Ishiguro T, Hayashi M, Ueda S, Mori I, Niimi K, Tashiro F, Miyazaki S, et al. Tip-cell behavior is regulated by transcription factor FoxO1 under hypoxic conditions in developing mouse retinas. Angiogenesis. 2018;21(2):203–14.PubMedCrossRef
7.
Abukar Y, Ramchandra R, Hood SG, McKinley MJ, Booth LC, Yao ST, May CN. Increased cardiac sympathetic nerve activity in ovine heart failure is reduced by lesion of the area postrema, but not lamina terminalis. Basic Res Cardiol. 2018;113(5):35.PubMedCrossRef
8.
Abeysuriya RG, Lockley SW, Robinson PA, Postnova S. A unified model of melatonin, 6-sulfatoxymelatonin, and sleep dynamics. J Pineal Res. 2018;64(4):e12474.PubMedCrossRef
9.
Garcia-Rendueles ME, Ricarte-Filho JC, Untch BR, Landa I, Knauf JA, Voza F, Smith VE, Ganly I, Taylor BS, Persaud Y, et al. NF2 loss promotes oncogenic RAS-induced thyroid cancers via YAP-dependent transactivation of RAS proteins and sensitizes them to MEK inhibition. Cancer Discov. 2015;5(11):1178–93.PubMedPubMedCentralCrossRef
10.
Lee SJ, Lee MH, Kim DW, Lee S, Huang S, Ryu MJ, Kim YK, Kim SJ, Kim SJ, Hwang JH, et al. Cross-regulation between oncogenic BRAF(V600E) kinase and the MST1 pathway in papillary thyroid carcinoma. PLoS ONE. 2011;6(1):e16180.PubMedPubMedCentralCrossRef
11.
Lowe NM, Loughran S, Slevin NJ, Yap BK. Anaplastic thyroid cancer: the addition of systemic chemotherapy to radiotherapy led to an observed improvement in survival—a single centre experience and review of the literature. Sci World J. 2014;2014:674583.CrossRef
12.
Gianni-Barrera R, Butschkau A, Uccelli A, Certelli A, Valente P, Bartolomeo M, Groppa E, Burger MG, Hlushchuk R, Heberer M, et al. PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation. Angiogenesis. 2018;21(4):883–900.PubMedPubMedCentralCrossRef
13.
Coverstone ED, Bach RG, Chen L, Bierut LJ, Li AY, Lenzini PA, O’Neill HC, Spertus JA, Sucharov CC, Stitzel JA, et al. A novel genetic marker of decreased inflammation and improved survival after acute myocardial infarction. Basic Res Cardiol. 2018;113(5):38.PubMedPubMedCentralCrossRef
14.
Brazao V, Colato RP, Santello FH, Vale GTD, Gonzaga NA, Tirapelli CR, Prado JCD Jr. Effects of melatonin on thymic and oxidative stress dysfunctions during Trypanosoma cruzi infection. J Pineal Res. 2018;65(3):e12510.PubMedCrossRef
15.
Ba X, Boldogh I. 8-Oxoguanine DNA glycosylase 1: beyond repair of the oxidatively modified base lesions. Redox Biol. 2018;14:669–78.PubMedCrossRef
16.
Biernacki M, Ambrozewicz E, Gegotek A, Toczek M, Bielawska K, Skrzydlewska E. Redox system and phospholipid metabolism in the kidney of hypertensive rats after FAAH inhibitor URB597 administration. Redox Biol. 2018;15:41–50.PubMedCrossRef
17.
Davidson SM, Arjun S, Basalay MV, Bell RM, Bromage DI, Botker HE, Carr RD, Cunningham J, Ghosh AK, Heusch G, et al. The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection-evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology. Basic Res Cardiol. 2018;113(6):43.PubMedPubMedCentralCrossRef
18.
Gonzalez NR, Liou R, Kurth F, Jiang H, Saver J. Antiangiogenesis and medical therapy failure in intracranial atherosclerosis. Angiogenesis. 2018;21(1):23–35.PubMedCrossRef
19.
DeLeon-Pennell KY, Mouton AJ, Ero OK, Ma Y, Padmanabhan Iyer R, Flynn ER, Espinoza I, Musani SK, Vasan RS, Hall ME, et al. LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling. Basic Res Cardiol. 2018;113(5):40.PubMedPubMedCentralCrossRef
20.
Yao S, Yan W. Overexpression of Mst1 reduces gastric cancer cell viability by repressing the AMPK-Sirt3 pathway and activating mitochondrial fission. Onco Targets Ther. 2018;11:8465–79.PubMedPubMedCentralCrossRef
21.
Chandra M, Escalante-Alcalde D, Bhuiyan MS, Orr AW, Kevil C, Morris AJ, Nam H, Dominic P, McCarthy KJ, Miriyala S, et al. Cardiac-specific inactivation of LPP3 in mice leads to myocardial dysfunction and heart failure. Redox Biol. 2018;14:261–71.PubMedCrossRef
22.
Korbel C, Gerstner MD, Menger MD, Laschke MW. Notch signaling controls sprouting angiogenesis of endometriotic lesions. Angiogenesis. 2018;21(1):37–46.PubMedCrossRef
23.
Edwards KS, Ashraf S, Lomax TM, Wiseman JM, Hall ME, Gava FN, Hall JE, Hosler JP, Harmancey R. Uncoupling protein 3 deficiency impairs myocardial fatty acid oxidation and contractile recovery following ischemia/reperfusion. Basic Res Cardiol. 2018;113(6):47.PubMedPubMedCentralCrossRef
24.
Yu R, Liu T, Jin SB, Ning C, Lendahl U, Nister M, Zhao J. MIEF1/2 function as adaptors to recruit Drp1 to mitochondria and regulate the association of Drp1 with Mff. Sci Rep. 2017;7(1):880.PubMedPubMedCentralCrossRef
25.
Zhou J, Zhang S, Li Z, Chen Z, Xu Y, Ye W, He Z. Yap-Hippo promotes A549 lung cancer cell death via modulating MIEF1-related mitochondrial stress and activating JNK pathway. Biomed Pharmacother. 2019;113:108754.PubMedCrossRef
26.
Fan T, Pi H, Li M, Ren Z, He Z, Zhu F, Tian L, Tu M, Xie J, Liu M, et al. Inhibiting MT2-TFE3-dependent autophagy enhances melatonin-induced apoptosis in tongue squamous cell carcinoma. J Pineal Res. 2018;64(2):e12457.CrossRef
27.
Fernandez Vazquez G, Reiter RJ, Agil A. Melatonin increases brown adipose tissue mass and function in Zucker diabetic fatty rats: implications for obesity control. J Pineal Res. 2018;64(4):e12472.PubMedCrossRef
28.
Chen T, Dai SH, Li X, Luo P, Zhu J, Wang YH, Fei Z, Jiang XF. Sirt1–Sirt3 axis regulates human blood–brain barrier permeability in response to ischemia. Redox Biol. 2018;14:229–36.PubMedCrossRef
29.
Li J, Cai SX, He Q, Zhang H, Friedberg D, Wang F, Redington AN. Intravenous miR-144 reduces left ventricular remodeling after myocardial infarction. Basic Res Cardiol. 2018;113(5):36.PubMedCrossRef
30.
Sajib S, Zahra FT, Lionakis MS, German NA, Mikelis CM. Mechanisms of angiogenesis in microbe-regulated inflammatory and neoplastic conditions. Angiogenesis. 2018;21(1):1–14.PubMedCrossRef
31.
32.
Souza LEB, Beckenkamp LR, Sobral LM, Fantacini DMC, Melo FUF, Borges JS, Leopoldino AM, Kashima S, Covas DT. Pre-culture in endothelial growth medium enhances the angiogenic properties of adipose-derived stem/stromal cells. Angiogenesis. 2018;21(1):15–22.PubMedCrossRef
33.
Zhou H, Li D, Zhu P, Hu S, Hu N, Ma S, Zhang Y, Han T, Ren J, Cao F, et al. Melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARgamma/FUNDC1/mitophagy pathways. J Pineal Res. 2017;63(4):e12438.CrossRef
34.
Nawaz IM, Chiodelli P, Rezzola S, Paganini G, Corsini M, Lodola A, Di Ianni A, Mor M, Presta M. N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic activity of heparin-binding growth factors. Angiogenesis. 2018;21(1):47–59.PubMedCrossRef
35.
Kiel AM, Goodwill AG, Baker HE, Dick GM, Tune JD. Local metabolic hypothesis is not sufficient to explain coronary autoregulatory behavior. Basic Res Cardiol. 2018;113(5):33.PubMedPubMedCentralCrossRef
36.
Krause J, Loser A, Lemoine MD, Christ T, Scherschel K, Meyer C, Blankenberg S, Zeller T, Eschenhagen T, Stenzig J. Rat atrial engineered heart tissue: a new in vitro model to study atrial biology. Basic Res Cardiol. 2018;113(5):41.PubMedCrossRef
37.
Giatsidis G, Cheng L, Haddad A, Ji K, Succar J, Lancerotto L, Lujan-Hernandez J, Fiorina P, Matsumine H, Orgill DP. Noninvasive induction of angiogenesis in tissues by external suction: sequential optimization for use in reconstructive surgery. Angiogenesis. 2018;21(1):61–78.PubMedCrossRef
38.
Hardeland R. Melatonin and inflammation-story of a double-edged blade. J Pineal Res. 2018;65(4):e12525.PubMedCrossRef
39.
Kanwar MK, Yu J, Zhou J. Phytomelatonin: recent advances and future prospects. J Pineal Res. 2018;65(4):e12526.PubMedCrossRef
40.
Zhou H, Yue Y, Wang J, Ma Q, Chen Y. Melatonin therapy for diabetic cardiomyopathy: a mechanism involving Syk-mitochondrial complex I-SERCA pathway. Cell Signal. 2018;47:88–100.PubMedCrossRef
41.
Jung M, Dodsworth M, Thum T. Inflammatory cells and their non-coding RNAs as targets for treating myocardial infarction. Basic Res Cardiol. 2018;114(1):4.PubMedPubMedCentralCrossRef
42.
Hobson SR, Gurusinghe S, Lim R, Alers NO, Miller SL, Kingdom JC, Wallace EM. Melatonin improves endothelial function in vitro and prolongs pregnancy in women with early-onset preeclampsia. J Pineal Res. 2018;65(3):e12508.PubMedCrossRef
43.
Zhou H, Zhu P, Guo J, Hu N, Wang S, Li D, Hu S, Ren J, Cao F, Chen Y. Ripk3 induces mitochondrial apoptosis via inhibition of FUNDC1 mitophagy in cardiac IR injury. Redox Biol. 2017;13:498–507.PubMedPubMedCentralCrossRef
44.
Li R, Xin T, Li D, Wang C, Zhu H, Zhou H. Therapeutic effect of Sirtuin 3 on ameliorating nonalcoholic fatty liver disease: the role of the ERK-CREB pathway and Bnip3-mediated mitophagy. Redox Biol. 2018;18:229–43.PubMedPubMedCentralCrossRef
45.
Kazakov A, Hall RA, Werner C, Meier T, Trouvain A, Rodionycheva S, Nickel A, Lammert F, Maack C, Bohm M, et al. Raf kinase inhibitor protein mediates myocardial fibrosis under conditions of enhanced myocardial oxidative stress. Basic Res Cardiol. 2018;113(6):42.PubMedPubMedCentralCrossRef
46.
Zhou H, Zhu P, Wang J, Zhu H, Ren J, Chen Y. Pathogenesis of cardiac ischemia reperfusion injury is associated with CK2alpha-disturbed mitochondrial homeostasis via suppression of FUNDC1-related mitophagy. Cell Death Differ. 2018;25(6):1080–93.PubMedPubMedCentralCrossRef
47.
Wang B, Yee Aw T, Stokes KY. N-acetylcysteine attenuates systemic platelet activation and cerebral vessel thrombosis in diabetes. Redox Biol. 2018;14:218–28.PubMedCrossRef
48.
Zhou H, Li N, Yuan Y, Jin YG, Guo H, Deng W, Tang QZ. Activating transcription factor 3 in cardiovascular diseases: a potential therapeutic target. Basic Res Cardiol. 2018;113(5):37.PubMedCrossRef
49.
Li H, Fu L, Liu B, Lin X, Dong Q, Wang E. Ajuba overexpression regulates mitochondrial potential and glucose uptake through YAP/Bcl-xL/GLUT1 in human gastric cancer. Gene. 2019;693:16–24.PubMedCrossRef
50.
51.
Merz J, Albrecht P, von Garlen S, Ahmed I, Dimanski D, Wolf D, Hilgendorf I, Hardtner C, Grotius K, Willecke F, et al. Purinergic receptor Y2 (P2Y2)-dependent VCAM-1 expression promotes immune cell infiltration in metabolic syndrome. Basic Res Cardiol. 2018;113(6):45.PubMedCrossRef
52.
Shi C, Cai Y, Li Y, Li Y, Hu N, Ma S, Hu S, Zhu P, Wang W, Zhou H. Yap promotes hepatocellular carcinoma metastasis and mobilization via governing cofilin/F-actin/lamellipodium axis by regulation of JNK/Bnip3/SERCA/CaMKII pathways. Redox Biol. 2018;14:59–71.PubMedCrossRef
53.
Li X, Brestic M, Tan DX, Zivcak M, Zhu X, Liu S, Song F, Reiter RJ, Liu F. Melatonin alleviates low PS I-limited carbon assimilation under elevated CO2 and enhances the cold tolerance of offspring in chlorophyll b-deficient mutant wheat. J Pineal Res. 2018;64(1):e12453.CrossRef
54.
Olson KR, Gao Y, Arif F, Arora K, Patel S, DeLeon ER, Sutton TR, Feelisch M, Cortese-Krott MM, Straub KD. Metabolism of hydrogen sulfide (H2S) and production of reactive sulfur species (RSS) by superoxide dismutase. Redox Biol. 2018;15:74–85.PubMedCrossRef
55.
Lu C, Chen X, Wang Q, Xu X, Xu B. TNFalpha promotes glioblastoma A172 cell mitochondrial apoptosis via augmenting mitochondrial fission and repression of MAPK-ERK-YAP signaling pathways. Onco Targets Ther. 2018;11:7213–27.PubMedPubMedCentralCrossRef
56.
Zhu P, Hu S, Jin Q, Li D, Tian F, Toan S, Li Y, Zhou H, Chen Y. Ripk3 promotes ER stress-induced necroptosis in cardiac IR injury: a mechanism involving calcium overload/XO/ROS/mPTP pathway. Redox Biol. 2018;16:157–68.PubMedPubMedCentralCrossRef
57.
Shi C, Zhou H, Li X, Cai Y. A retrospective analysis on two-week short-course pre-operative radiotherapy in elderly patients with resectable locally advanced rectal cancer. Sci Rep. 2016;6:37866.PubMedPubMedCentralCrossRef
58.
Oh SE, Mouradian MM. Cytoprotective mechanisms of DJ-1 against oxidative stress through modulating ERK1/2 and ASK1 signal transduction. Redox Biol. 2018;14:211–7.PubMedCrossRef
59.
Ding M, Ning J, Feng N, Li Z, Liu Z, Wang Y, Wang Y, Li X, Huo C, Jia X, et al. Dynamin-related protein 1-mediated mitochondrial fission contributes to post-traumatic cardiac dysfunction in rats and the protective effect of melatonin. J Pineal Res. 2018;64(1):e12447.CrossRef
60.
Park HJ, Park JY, Kim JW, Yang SG, Jung JM, Kim MJ, Kang MJ, Cho YH, Wee G, Yang HY, et al. Melatonin improves the meiotic maturation of porcine oocytes by reducing endoplasmic reticulum stress during in vitro maturation. J Pineal Res. 2018;64(2):e12458.PubMedCrossRef
61.
Alessio N, Del Gaudio S, Capasso S, Di Bernardo G, Cappabianca S, Cipollaro M, Peluso G, Galderisi U. Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process. Oncotarget. 2015;6(10):8155–66.PubMedCrossRef
Metadata
Title
RETRACTED ARTICLE: Mst1 overexpression combined with Yap knockdown augments thyroid carcinoma apoptosis via promoting MIEF1-related mitochondrial fission and activating the JNK pathway
Authors
Xiaoli Zhang
Fei Li
Yeqing Cui
Shuang Liu
Haichen Sun
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0860-8

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue

Primary research

hnRNPK promotes gastric tumorigenesis through regulating CD44E alternative splicing

Primary research

RASSF-1A modulates proliferation-mediated oral squamous cell carcinoma progression

Primary research

Integrated analyses of microRNA-29 family and the related combination biomarkers demonstrate their widespread influence on risk, recurrence, metastasis and survival outcome in colorectal cancer

Primary research

A DAAM1 3′-UTR SNP mutation regulates breast cancer metastasis through affecting miR-208a-5p-DAAM1-RhoA axis

Primary research

Mutual regulation of JAG2 and PRAF2 promotes migration and invasion of colorectal cancer cells uncoupled from epithelial–mesenchymal transition

Primary research

Identification of DNA methylation-driven genes in esophageal squamous cell carcinoma: a study based on The Cancer Genome Atlas
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