Nuclear localization of Nm23‐H1 in head and neck squamous cell carcinoma is associated with radiation resistance

Park, Haeng Ran; Kim, Se Heon; Lee, Sei Young; Sung, Ji Min; Park, Ae Ran; Kang, Suki; Kim, Baek Gil; Choi, Yoon Young; Kim, Yong Bae; Cho, Nam Hoon

doi:10.1002/cncr.25760

Cited by 24 publications

(7 citation statements)

References 66 publications

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“…Phosphorylated FAK is involve in activation of many signal transduction molecules and affects several cellular biological behaviors (She et al, 2010). Over expression of Nm23-H1, specifically its nuclear translocation may be a powerful predictor of radiation resistance in head and neck squamous cell carcinoma (HNSCC) (Park et al, 2010). Understanding the Nm23 gene expression could develop an effective method for targeting metastatic cascade and inhibition of tumor progression that could be a novel potential therapeutic strategy for cancer.…”

Section: Resultsmentioning

confidence: 99%

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Prabhu

Siddikuzzaman²,

Grace³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Prabhu

Siddikuzzaman²,

Grace³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…Seven oral cancer cell lines- SCC25, QLL1 (From Dr. Park, Yonsei University College of Medicine, Korea [23] & Dr Rheinwald, Harvard Medical School, Boston [24] ); UPCI:SCC029B, UPCI:SCC040 & UPCI:SCC074 (From Dr. S Gollin, University of Pittsburgh, PA) [25] ; AW8507 & AW13516 [26] were used in the study. Additionally an immortalized Fetal Buccal Mucosa (FBM) [27] and a Dysplastic Oral Keratinocyte (DOK) (from Dr. Ken Parkinson, Queen Mary's School of Medicine & Dentistry, UK) [28] cell lines were also used in study.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally an immortalized Fetal Buccal Mucosa (FBM) [27] and a Dysplastic Oral Keratinocyte (DOK) (from Dr. Ken Parkinson, Queen Mary's School of Medicine & Dentistry, UK) [28] cell lines were also used in study. The cells were maintained in MEM or IMDM supplemented with 10% FBS & 1% standard antibiotic mixture in 5% CO 2 incubator at 37°C as described earlier [17] , [23] , [29] .…”

Section: Methodsmentioning

confidence: 99%

Overexpression of Mcl-1L Splice Variant Is Associated with Poor Prognosis and Chemoresistance in Oral Cancers

et al. 2014

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BackgroundAltered expression of Mcl-1, an anti-apoptotic member of the Bcl-2 family, has been linked to the progression and outcome of a variety of malignancies. We have previously reported the overexpression of Mcl-1 protein in human oral cancers. The present study aimed to evaluate the clinicopathological significance of the expression of three known Mcl-1 isoforms in oral tumors and the effect of targeting Mcl-1L isoform on chemosensitivity of oral cancer cells.MethodsThe expression of Mcl-1 isoforms- Mcl-1L, Mcl-1S & Mcl-1ES was analyzed in 130 paired oral tumors and 9 oral cell lines using quantitative real-time PCR & protein by western blotting. The Mcl-1 mRNA levels were correlated with clinicopathological parameters and outcome of oral cancer patients. The effect of Mcl-1L shRNA or Obatoclax (a small molecule Mcl-1 inhibitor), in combination with Cisplatin on chemosensitivity of oral cancer cells was also assessed.ResultsAnti-apoptotic Mcl-1L was predominantly expressed, over low or undetectable pro-apoptotic Mcl-1S and Mcl-1ES isoforms. The Mcl-1L transcripts were significantly overexpressed in all cancer cell lines and in 64% oral tumors versus adjacent normals (P<0.02). In oral cancer patients, high Mcl-1L expression was significantly associated with node positivity (P = 0.021), advanced tumor size (P = 0.013) and poor overall survival (P = 0.002). Multivariate analysis indicated Mcl-1L to be an independent prognostic factor for oral cancers (P = 0.037). Mcl-1L shRNA knockdown or its inhibition by Obatoclax in combination with Cisplatin synergistically reduced viability and growth of oral cancer cells than either treatment alone.ConclusionOur studies suggest that overexpression of Mcl-1L is associated with poor prognosis and chemoresistance in oral cancers. Mcl-1L is an independent prognostic factor and a potential therapeutic target in oral cancers.

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“…Sheng and coworkers suggested that NME1 enters the nucleus after DNA damage and possibly takes part in several DNA-repair mechanisms [64]. It has even been suggested by Park and coworkers that the nuclear localization of NME1 in head and neck squamous cell carcinoma could be associated with radiation resistance [67] and, therefore, serve as a strong radiation resistance predictor. Similar research has been reported on human nasopharyngeal carcinoma [68] and oral squamous cell carcinoma [69].…”

Section: Nme1 and Nme2 Translocate To The Nucleus After Gamma Irradiamentioning

confidence: 99%

The Subcellular Localization and Oligomerization Preferences of NME1/NME2 upon Radiation-Induced DNA Damage

Radić

Šoštar

Weber

et al. 2020

IJMS

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Nucleoside diphosphate kinases (NDPK/NME/Nm23) are enzymes composed of subunits NME1/NDPK A and NME2/NDPK B, responsible for the maintenance of the cellular (d)NTP pool and involved in other cellular processes, such as metastasis suppression and DNA damage repair. Although eukaryotic NDPKs are active only as hexamers, it is unclear whether other NME functions require the hexameric form, and how the isoenzyme composition varies in different cellular compartments. To examine the effect of DNA damage on intracellular localization of NME1 and NME2 and the composition of NME oligomers in the nucleus and the cytoplasm, we used live-cell imaging and the FRET/FLIM technique. We showed that exogenous NME1 and NME2 proteins co-localize in the cytoplasm of non-irradiated cells, and move simultaneously to the nucleus after gamma irradiation. The FRET/FLIM experiments imply that, after DNA damage, there is a slight shift in the homomer/heteromer balance between the nucleus and the cytoplasm. Collectively, our results indicate that, after irradiation, NME1 and NME2 engage in mutual functions in the nucleus, possibly performing specific functions in their homomeric states. Finally, we demonstrated that fluorophores fused to the N-termini of NME polypeptides produce the largest FRET effect and thus recommend this orientation for use in similar studies.

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Nuclear localization of Nm23‐H1 in head and neck squamous cell carcinoma is associated with radiation resistance

Cited by 24 publications

References 66 publications

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Overexpression of Mcl-1L Splice Variant Is Associated with Poor Prognosis and Chemoresistance in Oral Cancers

The Subcellular Localization and Oligomerization Preferences of NME1/NME2 upon Radiation-Induced DNA Damage

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