| Title: |
TLR9 re-expression in cancer cells extends the S-phase and stabilizes p16(INK4a) protein expression |
| Authors: |
Parroche, Peggy; Roblot, Guillaume; Le Calvez-Kelm, Florence; Tout, Issam; Marotel, Marie; Malfroy, M.; Durand, Geoffroy; Mckay, James; Ainouze, Michelle; Carreira, C.; Allatif, Omran; Traverse-Glehen, A.; Mendiola, M.; Pozo-Kreilinger, J.J.; Caux, Christophe; Tommasino, M.; Goutagny, N.; Hasan, Uzma |
| Contributors: |
Immunité et lymphocytes cytotoxiques – Immunity and cytotoxic lymphocytes CIRI; Centre International de Recherche en Infectiologie (CIRI); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Réponse immunitaire innée dans les maladies infectieuses et auto-immunes – Innate immunity in infectious and autoimmune diseases CIRI; Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC); Organisation Mondiale de la Santé / World Health Organization Office Genève, Suisse (OMS / WHO); Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL); Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Laboratoire d'anatomie et de cytopathologie - Centre hospitalier Lyon Sud; Hospices Civils de Lyon (HCL); Hospital Universitario La Paz-Carlos III Madrid; La Paz University Hospital |
| Source: |
ISSN: 2157-9024. |
| Publisher Information: |
CCSD; Open Access Journals - Option C |
| Publication Year: |
2016 |
| Collection: |
Université Jean Monnet – Saint-Etienne: HAL |
| Subject Terms: |
Epithelial Cells; Cell Cycle; Carcinogenesis; France; pathology; Time; Dna; Cells; genetics; Gene Expression Profiling; Growth; Apoptosis; Gene Expression; Cell Proliferation; analysis; Necrosis; [SDV.CAN]Life Sciences [q-bio]/Cancer |
| Description: |
International audience ; Toll-like receptor 9 (TLR9) recognizes bacterial, viral or cell damage-associated DNA, which initiates innate immune responses. We have previously shown that TLR9 expression is downregulated in several viral induced cancers including HPV16-induced cervical neoplasia. Findings supported that downregulation of TLR9 expression is involved in loss of anti-viral innate immunity allowing an efficient viral replication. Here we investigated the role of TLR9 in altering the growth of transformed epithelial cells. Re-introducing TLR9 under the control of an exogenous promoter in cervical or head and neck cancer patient-derived cells reduced cell proliferation, colony formation and prevented independent growth of cells under soft agar. Neither TLR3, 7, nor the TLR adapter protein MyD88 expression had any effect on cell proliferation, indicating that TLR9 has a unique role in controlling cell growth. The reduction of cell growth was not due to apoptosis or necrosis, yet we observed that cells expressing TLR9 were slower in entering the S-phase of the cell cycle. Microarray-based gene expression profiling analysis highlighted a strong interferon (IFN) signature in TLR9-expressing head and neck cancer cells, with an increase in IFN-type I and IL-29 expression (IFN-type III), yet neither IFN-type I nor IL-29 production was responsible for the block in cell growth. We observed that the protein half-life of p16(INK4a) was increased in TLR9-expressing cells. Taken together, these data show for the first time that TLR9 affects the cell cycle by regulating p16(INK4a) post-translational modifications and highlights the role of TLR9 in the events that lead to carcinogenesis |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/27454079; PUBMED: 27454079; PUBMEDCENTRAL: PMC4972902 |
| DOI: |
10.1038/oncsis.2016.49 |
| Availability: |
https://hal.science/hal-01812689; https://doi.org/10.1038/oncsis.2016.49 |
| Accession Number: |
edsbas.528DB7F2 |
| Database: |
BASE |