title: Small proline-rich protein-1B is overexpressed in human oral squamous cell cancer stem-like cells and is related to their growth through activation of MAP kinase signal.
abstract: Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are considered to be essential for tumor maintenance, recurrence and metastasis. Therefore, eradication of CSCs/CICs is essential to cure cancers. However, the molecular mechanisms of CSCs/CICs are still elusive. In this study, we investigated the molecular mechanism of the cell growth of oral CSCs/CICs. Oral CSCs/CICs were isolated as aldehyde dehydrogenase 1 bright (ALDH1(br)) cells by the ALDEFLUOR assay. Small proline-rich protein-1B (SPRR1B) gene was shown to be overexpressed in ALDH1(br) cells by a cDNA microarray and RT-PCR. SPRR1B was shown to have a role in cell growth and maintenance of ALDH1(br) cells by SPRR1B overexpression and knockdown experiments. To elucidate the molecular mechanism by which SPRR1B regulates cell growth, further cDNA microarray analysis was performed using SPRR1B-overexpressed cells and cells with SPRR1B knocked down by siRNA. Expression of the tumor suppressor gene Ras association domain family member 4 (RASSF4) was found to be suppressed in SPRR1B-overexpressed cells. On the other hand, the expression of RASSF4 was enhanced in cells in which SPRR1B expression was knocked down by SPRR1B-specific siRNA. RASSF4 has an RA (Ras association) domain, and we thus hypothesized that RASSF4 modulates the MAP kinase signal downstream of the Ras signal. MAP kinase signal was activated in SPRR1B-overexpressed cells, whereas the signal was suppressed in SPRR1B knocked down cells. Taken together, the results indicate that the expression of SPRR1B is upregulated in oral CSCs/CICs and that SPRR1B has a role in cell growth by suppression of RASSF4.
authors: Department of Pathology, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan; Department of Oral Surgery, Sapporo Medical University School of Medicine, South-1 West-17, Chuo-ku, Sapporo 060-8556, Japan.
authors: Yoshitaka
authors: Y
authors: Michifuri
authors: Yoshihiko
authors: Y
authors: Hirohashi
authors: Toshihiko
authors: T
authors: Torigoe
authors: Akihiro
authors: A
authors: Miyazaki
authors: Jyunki
authors: J
authors: Fujino
authors: Yasuaki
authors: Y
authors: Tamura
authors: Tomohide
authors: T
authors: Tsukahara
authors: Takayuki
authors: T
authors: Kanaseki
authors: Junichi
authors: J
authors: Kobayashi
authors: Takanori
authors: T
authors: Sasaki
authors: Akari
authors: A
authors: Takahashi
authors: Kenji
authors: K
authors: Nakamori
authors: Akira
authors: A
authors: Yamaguchi
authors: Hiroyoshi
authors: H
authors: Hiratsuka
authors: Noriyuki
authors: N
authors: Sato
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003094:Collagen / Q000737:chemistry; D055233:Cornified Envelope Proline-Rich Proteins / Q000378:metabolism*; D004338:Drug Combinations; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D007797:Laminin / Q000737:chemistry; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000378:metabolism*; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011509:Proteoglycans / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C495500:RASSF4 protein, human; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; C059485:matrigel; C524533:SPRR1B protein, human; D003094:Collagen; D000444:Aldehyde Dehydrogenase
keywords: ALDEFLUOR assay; CIC; CSC; Cancer stem cell; NOD/SCID; OSCC; Oral cancer; RASSF4; SPRR1B; cancer stem-like cell; cancer-initiating cell; non-obese diabetic/severe combined immunodeficiency; oral squamous cell carcinoma; ras association domain family member 4; small proline-rich protein-1B