Skip to main content
SpringerLink
Log in

Contribution of LATS1 and LATS2 promoter methylation in OSCC development

  • RESEARCH ARTICLE
  • Published:
Journal of Cell Communication and Signaling Aims and scope

Abstract

The aberrant DNA methylation of the tumor suppressor genes involved in DNA Damage Response (DDR) signaling and cell cycle regulation may lead to the tumorigenesis. Our purpose here is to analyze the promoter methylation and mRNA expression levels of LATS1 and LATS2 (LATS1/2) genes in OSCC. Promoter methylation status of LATS1/2 genes was evaluated in 70 OSCC paraffin-embedded tissues and 70 normal oral samples, using Methylation Specific PCR (MSP). LATS1/2 mRNA expression profiles were also investigated in 14 OSCC patients and 14 normal samples, using real-time PCR. In both candidate genes, promoter methylation assessment revealed significant relationship between cases and controls (OR = 2.24, 95 % CI = 1.40–3.54, P = 0.001; LATS1 and OR = 15.5, 95%CI = 3.64–64.76, P < 0.001; LATS2). As well as, the evaluation of mRNA expression levels showed decreased expression in OSCC tissues in compare to control tissues. (Mean ± SD 1.74 ± 0.14 in OSCC versus 2.10 ± 0.24 in controls, P < 0.001; LATS1 and Mean ± SD 1.36 ± 0.077 in OSCC versus 1.96 ± 0.096 in controls, P < 0.001; LATS2). To the best our knowledge, this is the first report regarding the down-regulation of LATS1/2 through promoter methylation in OSCC. It is suggested to explore the down-stream transcription factors of both genes for finding the molecular mechanism of this deregulation in OSCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aqeilan RI (2013) Hippo signaling: to die or not to die. Cell Death Differ 20:1287–1288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aylon Y, Michael D, Shmueli A, Yabuta N, Nojima H, Oren M (2006) A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization. Genes Dev 20:2687–2700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aylon Y, Ofir-Rosenfeld Y, Yabuta N, Lapi E, Nojima H, Lu X, Oren M (2010) The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1. Genes Dev 24:2420–2429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chien M-H, Liu Y-F, Hsin C-H, Lin C-H, Shih C-H, Yang S-F, Cheng C-W, Lin C-W (2013) Impact of VEGF-C Gene polymorphisms and environmental factors on oral cancer susceptibility in Taiwan. PLoS One 8:e60283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi S, Myers JN (2008) Molecular pathogenesis of oral squamous cell carcinoma: implications for therapy. J Dent Res 87:14–32

    Article  CAS  PubMed  Google Scholar 

  • Furth N, Oren M (2011) An aurora A-Lats-aurora B axis ensures proper chromosome segregation. Cell Cycle 10:3055

    Article  PubMed  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  • Jiang Z, Li X, Hu J, Zhou W, Jiang Y, Li G, Lu D (2006) Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma. Neurosci Res 56:450–458

    Article  CAS  PubMed  Google Scholar 

  • Kordi-Tamandani DM, Moazeni-Roodi A, Rigi Ladez MA, Hashemi M, Birjandian E, Torkamanzehi A (2010a) Analysis of methylation patterns and expression profiles of p14ARF gene in patients with oral squamous cell carcinoma. Int J Biol Markers 25:99–103

    CAS  PubMed  Google Scholar 

  • Kordi-Tamandani DM, Moazeni-Roodi AK, Rigi-Ladiz MA, Hashemi M, Birjandian E, Torkamanzehi A (2010b) Promoter hypermethylation and expression profile of MGMT and CDH1 genes in oral cavity cancer. Arch Oral Biol 55:809–814

    Article  CAS  PubMed  Google Scholar 

  • Kordi-Tamandani DM, Ladies MA, Hashemi M, Moazeni-Roodi AK, Krishna S, Torkamanzehi A (2012) Analysis of p15INK4b and p16INK4a gene methylation in patients with oral squamous cell carcinoma. Biochem Genet 50:448–453

    Article  CAS  PubMed  Google Scholar 

  • Kordi-Tamandani DM, Saberi E, Jamali S, Ladiz MA (2014) ERK and RAF1 genes: analysis of methylation and expression profiles in patients with oral squamous cell carcinoma. Br J Biomed Sci 71:100–103

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Pei J, Xia H, Ke H, Wang H, Tao W (2003) Lats2, a putative tumor suppressor, inhibits G1/S transition. Oncogene 22:4398–4405

    Article  CAS  PubMed  Google Scholar 

  • Matallanas D, Romano D, Al-Mulla F, O'Neill E, Al-Ali W, Crespo P, Doyle B, Nixon C, Sansom O, Drosten M et al (2011) Mutant K-Ras activation of the proapoptotic MST2 pathway is antagonized by wild-type K-Ras. Mol Cell 44:893–906

    Article  CAS  PubMed  Google Scholar 

  • Mikeska T, Craig JM (2014) DNA methylation biomarkers: cancer and beyond. Genes 5:821–864

    Article  PubMed  PubMed Central  Google Scholar 

  • Najafi M, Kordi-Tamandani DM, Arish M (2016) Evaluation of LATS1 and LATS2 promoter methylation with the risk of pterygium formation. J Ophthalmol 2016:5431021

    Article  PubMed  PubMed Central  Google Scholar 

  • Okada N, Yabuta N, Suzuki H, Aylon Y, Oren M, Nojima H (2011) A novel Chk1/2-Lats2-14-3-3 signaling pathway regulates P-body formation in response to UV damage. J Cell Sci 124:57–67

    Article  CAS  PubMed  Google Scholar 

  • Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globocan 2000. Int J Cancer 94:153–156

    Article  CAS  PubMed  Google Scholar 

  • Perez-Sayans M, Somoza-Martin JM, Barros-Angueira F, Reboiras-Lopez MD, Gandara Rey JM, Garcia-Garcia A (2009) Genetic and molecular alterations associated with oral squamous cell cancer (review). Oncol Rep 22:1277

    Article  CAS  PubMed  Google Scholar 

  • Piccolo S, Dupont S, Cordenonsi M (2014) The biology of YAP/TAZ: hippo signaling and beyond. Physiol Rev 94:1287–1312

    Article  CAS  PubMed  Google Scholar 

  • Rad A, Farshchian M, Forghanifard MM, Matin MM, Bahrami AR, Geerts D (2016) A’rabi a, Memar B, Abbaszadegan MR: predicting the molecular role of MEIS1 in esophageal squamous cell carcinoma. Tumor Biol 37:1715–1725

    Article  CAS  Google Scholar 

  • Rigi-Ladiz MA, Kordi-Tamandani DM, Torkamanzehi A (2011) Analysis of hypermethylation and expression profiles of APC and ATM genes in patients with oral squamous cell carcinoma. Clin Epigenetics 3:6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saberi E, Kordi-Tamandani DM, Jamali S, Rigi-Ladiz MA (2014) Analysis of methylation and mRNA expression status of FADD and FAS genes in patients with oral squamous cell carcinoma. Med Oral Patol Oral Cir Bucal 19:e562–e568

    PubMed  PubMed Central  Google Scholar 

  • Sadasivam S, DeCaprio JA (2013) The DREAM complex: master coordinator of cell cycle-dependent gene expression. Nat Rev Cancer 13:585–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasaki H, Hikosaka Y, Kawano O, Yano M, Fujii Y (2010) Hypermethylation of the large tumor suppressor genes in Japanese lung cancer. Oncol Lett 1:303–307

    CAS  PubMed  PubMed Central  Google Scholar 

  • Scrace SF, O’Neill E (2012) RASSF Signalling and DNA damage: monitoring the integrity of the genome? Mol Biol Int 2012:141732

    Article  PubMed  PubMed Central  Google Scholar 

  • Suzuki H, Yabuta N, Okada N, Torigata K, Aylon Y, Oren M, Nojima H (2013) Lats2 phosphorylates p21/CDKN1A after UV irradiation and regulates apoptosis. J Cell Sci 126:4358–4368

    Article  CAS  PubMed  Google Scholar 

  • Takahashi Y, Miyoshi Y, Takahata C, Irahara N, Taguchi T, Tamaki Y, Noguchi S (2005) Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers. Clin Cancer Res 11:1380–1385

    Article  CAS  PubMed  Google Scholar 

  • Tuch BB, Laborde RR, Xu X, Gu J, Chung CB, Monighetti CK, Stanley SJ, Olsen KD, Kasperbauer JL, Moore EJ et al (2010) Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations. PLoS One 5:e9317

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang L, Mosel AJ, Oakley GG, Peng A (2012) Deficient DNA damage signaling leads to chemoresistance to cisplatin in oral cancer. Mol Cancer Ther 11:2401–2409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wierzbicki PM, Adrych K, Kartanowicz D, Stanislawowski M, Kowalczyk A, Godlewski J, Skwierz-Bogdanska I, Celinski K, Gach T, Kulig J et al (2013) Underexpression of LATS1 TSG in colorectal cancer is associated with promoter hypermethylation. World J Gastroenterol 19:4363–4373

    Article  PubMed  PubMed Central  Google Scholar 

  • Xia H, Qi H, Li Y, Pei J, Barton J, Blackstad M, Xu T, Tao W (2002) LATS1 tumor suppressor regulates G2/M transition and apoptosis. Oncogene 21:1233–1241

    Article  CAS  PubMed  Google Scholar 

  • Yabuta N, Mukai S, Okada N, Aylon Y, Nojima H (2011) The tumor suppressor Lats2 is pivotal in aurora a and aurora B signaling during mitosis. Cell Cycle 10:2724–2736

    Article  CAS  PubMed  Google Scholar 

  • Yabuta N, Mukai S, Okamoto A, Okuzaki D, Suzuki H, Torigata K, Yoshida K, Okada N, Miura D, Ito A et al (2013) N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability. J Cell Sci 126:508–520

    Article  CAS  PubMed  Google Scholar 

  • Yabuta N, Yoshida K, Mukai S, Kato Y, Torigata K, Nojima H (2016) Large tumor suppressors 1 and 2 regulate aurora-B through phosphorylation of INCENP to ensure completion of cytokinesis. Heliyon 2:e00131

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Q, Zhang J, Jin H, Sheng S (2013) Whole transcriptome sequencing identifies tumor-specific mutations in human oral squamous cell carcinoma. BMC Med Genet 6:28

    CAS  Google Scholar 

Download references

Acknowledgments

We kindly acknowledge to our colleagues in department of Ophthalmology, Al-Zahra Eye Hospital, Zahedan University of Medical Sciences, and in the department of Biology, University of Sistan and Baluchestan, for their technical supports.

Author information

Authors and Affiliations

  1. Oral and dental disease research center, Zahedan University of Medical Science, Zahedan, Iran

    Mohammad Ayoub Rigi Ladiz

  2. Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran

    Maryam Najafi

  3. Departement of Biology, University of Sistan and Baluchestan, P.O. Box 98155-987, Zahedan, Iran

    Maryam Najafi & Dor Mohammad Kordi-Tamandani

Authors
  1. Mohammad Ayoub Rigi Ladiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maryam Najafi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dor Mohammad Kordi-Tamandani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dor Mohammad Kordi-Tamandani.

Ethics declarations

Conflicts of interest

The authors declare no conflict of interest.

Research involving human participants

All procedures performed in studies involving human participants was in accordance with the ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ladiz, M.A.R., Najafi, M. & Kordi-Tamandani, D.M. Contribution of LATS1 and LATS2 promoter methylation in OSCC development. J. Cell Commun. Signal. 11, 49–55 (2017). https://doi.org/10.1007/s12079-016-0356-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12079-016-0356-4

Keywords

Search

Navigation