RGD Reference Report - Down-regulation of tumor suppressor MTUS1/ATIP is associated with enhanced proliferation, poor differentiation and poor prognosis in oral tongue squamous cell carcinoma. - Rat Genome Database

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Down-regulation of tumor suppressor MTUS1/ATIP is associated with enhanced proliferation, poor differentiation and poor prognosis in oral tongue squamous cell carcinoma.

Authors: Ding, Xueqiang  Zhang, Ningning  Cai, Yushen  Li, Su  Zheng, Chaoxu  Jin, Yi  Yu, Tianwei  Wang, Anxun  Zhou, Xiaofeng 
Citation: Ding X, etal., Mol Oncol. 2012 Feb;6(1):73-80. doi: 10.1016/j.molonc.2011.11.002. Epub 2011 Nov 18.
RGD ID: 25330347
Pubmed: PMID:22153618   (View Abstract at PubMed)
PMCID: PMC3268820   (View Article at PubMed Central)
DOI: DOI:10.1016/j.molonc.2011.11.002   (Journal Full-text)

Microtubule-associated tumor suppressor gene (MTUS1, also known as mitochondrial tumor suppressor) is a recently identified tumor suppressor gene that has been implicated in several cancer types. The expression of MTUS1 gene leads to 5 known transcript variants and codes for 5 isoforms of Angiotensin II AT2 receptor interacting protein (ATIP). In this study, we first confirmed that the down-regulation of MTUS1/ATIP was a frequent event in oral tongue squamous cell carcinoma (OTSCC) and the premalignant lesion (leukoplakia). We further demonstrated that the down-regulation of MTUS1/ATIP was correlated with poor differentiation and enhanced proliferation (Ki67 proliferation index). Statistical analysis suggests that the down-regulation of MTUS1/ATIP was associated with reduced overall survival. Isoform specific quantitative RT-PCR assays revealed that ATIP1, ATIP3a and ATIP3b were the major isoforms of the MTUS1 gene products in oral tongue epithelial cells. Significant down-regulations were observed for all 3 ATIP isoforms in OTSCC as compared to matching normal tissues. In vitro functional study showed that the restoration of ATIP1 expression led to G1 arrest, apoptosis and reduction of cell proliferation in OTSCC cell lines. These ATIP1-induced cellular changes were accompanied by reduced phosphorylation of ERK1/2 and up-regulation of p53. Taken together, these data suggest that MTUS1 plays major roles in the progression of OTSCC, and may serve as a biomarker or therapeutic target for patients with OTSCC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
tongue squamous cell carcinoma disease_progressionIEP 25330347 RGD 
tongue squamous cell carcinoma disease_progressionISOMTUS1 (Homo sapiens)25330347; 25330347 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mtus1  (microtubule associated scaffold protein 1)

Genes (Mus musculus)
Mtus1  (mitochondrial tumor suppressor 1)

Genes (Homo sapiens)
MTUS1  (microtubule associated scaffold protein 1)


Additional Information