title: SPINDLIN1 promotes cancer cell proliferation through activation of WNT/TCF-4 signaling.
abstract: SPINDLIN1, a new member of the SPIN/SSTY gene family, was first identified as a gene highly expressed in ovarian cancer cells. We have previously shown that it is involved in the process of spindle organization and chromosomal stability and plays a role in the development of cancer. Nevertheless, the mechanisms underlying its oncogenic role are still largely unknown. Here, we first showed that expression of SPINDLIN1 is upregulated in clinical tumors. Ectopic expression of SPINDLIN1 promoted cancer cell proliferation and activated WNT/T-cell factor (TCF)-4 signaling. The Ser84 and Ser99 amino acids within SPINDLIN1 were further identified as the key functional sites in WNT/TCF-4 signaling activation. Mutation of these two sites of SPINDLIN1 abolished its effects on promoting WNT/TCF-4 signaling and cancer cell proliferation. We further found that Aurora-A could interact with and phosphorylate SPINDLIN1 at its key functional sites, Ser84 and Ser99, suggesting that phosphorylation of SPINDLIN1 is involved in its oncogenic function. Collectively, these results suggest that SPINDLIN1, which may be a novel substrate of the Aurora-A kinase, promotes cancer cell growth through WNT/TCF-4 signaling activation.
authors.affiliation: Stem Cell and Regenerative Medicine Laboratory, Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Jing-Xue
authors.initials: JX
authors.lastname: Wang
authors.forename: Quan
authors.initials: Q
authors.lastname: Zeng
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Ji-Chao
authors.initials: JC
authors.lastname: Du
authors.forename: Xin-Long
authors.initials: XL
authors.lastname: Yan
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Yuan
authors.forename: Chao
authors.initials: C
authors.lastname: Zhai
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zhou
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Jia
authors.forename: Wen
authors.initials: W
authors.lastname: Yue
authors.forename: Xue-Tao
authors.initials: XT
authors.lastname: Pei
mesh_terms: D064127:Aurora Kinases; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; C104434:spindlin; D010768:Phosphoserine; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases