title: SASS6 overexpression is associated with mitotic chromosomal abnormalities and a poor prognosis in patients with colorectal cancer.
abstract: Spindle assembly abnormal protein 6 homolog (SASS6) plays an important role in the regulation of centriole duplication. To date, the genetic alteration of SASS6 has not been reported in human cancers. In the present study, we examined whether SASS6 expression is abnormally regulated in colorectal cancers (CRCs). Increased SASS6 mRNA and protein expression levels were observed in 49 (60.5%) of the 81 primary CRCs and 11 (57.9%) of the 19 primary CRCs, respectively. Moreover, the upregulation of SASS6 mRNA expression was statistically significant (P=0.0410). Next, using DLD-1 colon cancer cells inducibly expressing SASS6, SASS6 overexpression was shown to induce centrosome amplification, mitotic abnormalities such as chromosomal misalignment and lagging chromosome, and chromosomal numerical changes. Furthermore, SASS6 overexpression was associated with anaphase bridge formation, a type of mitotic structural abnormality, in primary CRCs (P<0.01). SASS6 upregulation in colon cancer was also revealed in the Cancer Genome Atlas (TCGA) data and was shown to be an independent predictor of poor survival (multivariate analysis: hazard ratio, 2.805; 95% confidence interval, 1.244‑7.512; P=0.0112). Finally, further analysis of the TCGA data demonstrated SASS6 upregulation in a modest manner in 8 of 11 cancer types other than colon cancer, and SASS6 upregulation was found to be associated with a poor survival outcome in patients with kidney renal cell carcinoma and lung adenocarcinoma. Our present findings revealed that the upregulation of SASS6 expression is involved in the pathogenesis of CRC and is associated with a poor prognosis among patients with colon cancer. They also suggest that SASS6 upregulation is a genetic abnormality relatively common in human cancer.
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shinmura
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Hisami
authors.initials: H
authors.lastname: Kato
authors.affiliation: Research Equipment Center, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kawanishi
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Nagura
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Takaharu
authors.initials: T
authors.lastname: Kamo
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okubo
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Nobuya
authors.initials: N
authors.lastname: Kurabe
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Chunping
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Moriya
authors.initials: M
authors.lastname: Iwaizumi
authors.affiliation: Department of Surgery 2, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kurachi
authors.affiliation: Department of Surgery, Fujieda Municipal General Hospital, Fujieda, Shizuoka, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
mesh_terms: D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D002869:Chromosome Aberrations; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C497202:SASS6 protein, human