title: CD271 regulates the proliferation and motility of hypopharyngeal cancer cells.
abstract: CD271 (p75 neurotrophin receptor) plays both positive and negative roles in cancer development, depending on the cell type. We previously reported that CD271 is a marker for tumor initiation and is correlated with a poor prognosis in human hypopharyngeal cancer (HPC). To clarify the role of CD271 in HPC, we established HPC cell lines and knocked down the CD271 expression using siRNA. We found that CD271-knockdown completely suppressed the cells' tumor-forming capability both in vivo and in vitro. CD271-knockdown also induced cell-cycle arrest in G0 and suppressed ERK phosphorylation. While treatment with an ERK inhibitor only partially inhibited cell growth, CDKN1C, which is required for maintenance of quiescence, was strongly upregulated in CD271-depleted HPC cells, and the double knockdown of CD271 and CDKN1C partially rescued the cells from G0 arrest. In addition, either CD271 depletion or the inhibition of CD271-RhoA signaling by TAT-Pep5 diminished the in vitro migration capability of the HPC cells. Collectively, CD271 initiates tumor formation by increasing the cell proliferation capacity through CDKN1C suppression and ERK-signaling activation, and by accelerating the migration signaling pathway in HPC.
authors.affiliation: Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan.|Department of Oncovirology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Mochizuki
authors.affiliation: Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan.|Department of Cancer Stem Cell Research, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tamai
authors.affiliation: Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Imai
authors.affiliation: Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ogama
authors.affiliation: Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan.
authors.forename: Mao
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Japan.|Department of Head and Neck Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan.|Department of Oncovirology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan.|Department of Cancer Stem Cell Research, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kennichi
authors.initials: K
authors.lastname: Satoh
authors.affiliation: Department of Pathology, Miyagi Cancer Center, Natori, Japan.|Department of Cancer Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Ikuro
authors.initials: I
authors.lastname: Sato
authors.affiliation: Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Hozumi
authors.initials: H
authors.lastname: Motohashi
authors.affiliation: Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
authors.affiliation: Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Japan.|Department of Cancer Biology and Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tanaka
mesh_terms: D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor