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CAMSAP3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation

BACKGROUND: Cellular senescence is an aging‐related process found in cancer cells that contributes to irreversible growth arrest and tumor aggressiveness. Recently, calmodulin‐regulated spectrin‐associated protein 3 (CAMSAP3), a minus‐end microtubule‐stabilizing protein, has received increasing atte...

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Autores principales: Wattanathamsan, Onsurang, Chetprayoon, Paninee, Chantaravisoot, Naphat, Wongkongkathep, Piriya, Chanvorachote, Pithi, Pongrakhananon, Varisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683528/
https://www.ncbi.nlm.nih.gov/pubmed/34724356
http://dx.doi.org/10.1002/cam4.4380
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author Wattanathamsan, Onsurang
Chetprayoon, Paninee
Chantaravisoot, Naphat
Wongkongkathep, Piriya
Chanvorachote, Pithi
Pongrakhananon, Varisa
author_facet Wattanathamsan, Onsurang
Chetprayoon, Paninee
Chantaravisoot, Naphat
Wongkongkathep, Piriya
Chanvorachote, Pithi
Pongrakhananon, Varisa
author_sort Wattanathamsan, Onsurang
collection PubMed
description BACKGROUND: Cellular senescence is an aging‐related process found in cancer cells that contributes to irreversible growth arrest and tumor aggressiveness. Recently, calmodulin‐regulated spectrin‐associated protein 3 (CAMSAP3), a minus‐end microtubule‐stabilizing protein, has received increasing attention in cancer cell biology. However, the biological role of CAMSAP3 on senescence in human lung cancer remains incompletely understood. METHODS: The function of CAMSAP3 on the regulation of cellular senescence‐associated phenotypes in human non‐small cell lung cancer H460 cells were determined in CAMSAP3 deletion (H460/C3ko) cells. The effects of CAMSAP3 on cell proliferation were investigated using MTT and colony formation assays. The cell cycle activity was evaluated by flow cytometry and the senescence‐associated phenotypes were observed by SA‐β‐Gal staining. Quantitative RT‐PCR and westen blot were used to evaluate the expression of cell cycle and senescence markers. Moreover, the interaction of CAMSAP3‐ERK1/2 and possible partner protein was quantified using immunoprecipitation/mass spectrometry and immunofluorescence. Lastly, an xenograft model were performed. RESULTS: CAMSAP3 knockout promotes lung cancer cell senescence‐associated phenotypes and induces G1 cell cycle arrest. Mechanistic investigation revealed that phosphorylated ERK (p‐ERK) was markedly downregulated in CAMSAP3‐deleted cells, suppressing cyclin D1 expression levels, and full‐length CAMSAP3 abrogated these phenotypes. Proteomic analysis demonstrated that vimentin, an intermediate filament protein, is required as a scaffold for CAMSAP3‐modulating ERK signaling. Furthermore, an in vivo tumor xenograft experiment showed that tumor initiation is potentially delayed in CAMSAP3 knockout tumors with the downregulation of p‐ERK and cyclin D1, resulting in a senescence‐like phenotype. CONCLUSION: This study is the first to report an intriguing role of CAMSAP3 in lung carcinoma cell senescence‐associated phenotypes via the modulation of p‐ERK/cyclin D1 signaling.
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spelling pubmed-86835282021-12-30 CAMSAP3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation Wattanathamsan, Onsurang Chetprayoon, Paninee Chantaravisoot, Naphat Wongkongkathep, Piriya Chanvorachote, Pithi Pongrakhananon, Varisa Cancer Med Cancer Biology BACKGROUND: Cellular senescence is an aging‐related process found in cancer cells that contributes to irreversible growth arrest and tumor aggressiveness. Recently, calmodulin‐regulated spectrin‐associated protein 3 (CAMSAP3), a minus‐end microtubule‐stabilizing protein, has received increasing attention in cancer cell biology. However, the biological role of CAMSAP3 on senescence in human lung cancer remains incompletely understood. METHODS: The function of CAMSAP3 on the regulation of cellular senescence‐associated phenotypes in human non‐small cell lung cancer H460 cells were determined in CAMSAP3 deletion (H460/C3ko) cells. The effects of CAMSAP3 on cell proliferation were investigated using MTT and colony formation assays. The cell cycle activity was evaluated by flow cytometry and the senescence‐associated phenotypes were observed by SA‐β‐Gal staining. Quantitative RT‐PCR and westen blot were used to evaluate the expression of cell cycle and senescence markers. Moreover, the interaction of CAMSAP3‐ERK1/2 and possible partner protein was quantified using immunoprecipitation/mass spectrometry and immunofluorescence. Lastly, an xenograft model were performed. RESULTS: CAMSAP3 knockout promotes lung cancer cell senescence‐associated phenotypes and induces G1 cell cycle arrest. Mechanistic investigation revealed that phosphorylated ERK (p‐ERK) was markedly downregulated in CAMSAP3‐deleted cells, suppressing cyclin D1 expression levels, and full‐length CAMSAP3 abrogated these phenotypes. Proteomic analysis demonstrated that vimentin, an intermediate filament protein, is required as a scaffold for CAMSAP3‐modulating ERK signaling. Furthermore, an in vivo tumor xenograft experiment showed that tumor initiation is potentially delayed in CAMSAP3 knockout tumors with the downregulation of p‐ERK and cyclin D1, resulting in a senescence‐like phenotype. CONCLUSION: This study is the first to report an intriguing role of CAMSAP3 in lung carcinoma cell senescence‐associated phenotypes via the modulation of p‐ERK/cyclin D1 signaling. John Wiley and Sons Inc. 2021-11-01 /pmc/articles/PMC8683528/ /pubmed/34724356 http://dx.doi.org/10.1002/cam4.4380 Text en © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Cancer Biology
Wattanathamsan, Onsurang
Chetprayoon, Paninee
Chantaravisoot, Naphat
Wongkongkathep, Piriya
Chanvorachote, Pithi
Pongrakhananon, Varisa
CAMSAP3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation
title CAMSAP3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation
title_full CAMSAP3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation
title_fullStr CAMSAP3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation
title_full_unstemmed CAMSAP3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation
title_short CAMSAP3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation
title_sort camsap3 depletion induces lung cancer cell senescence‐associated phenotypes through extracellular signal‐regulated kinase inactivation
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8683528/
https://www.ncbi.nlm.nih.gov/pubmed/34724356
http://dx.doi.org/10.1002/cam4.4380
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