Radiation sensitization of tumor cells induced by shear stress: The roles of integrins and FAK

Chi Wen Luo, Chia-Ching Wu, Hui Ju Ch'ang

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Recent studies revealed that the interstitial fluid flow in and around tumor tissue not only played an important role in delivering anticancer agents, but also affected the microenvironment, mostly hypoxia, in modulating tumor radio-sensitivity. The current study investigated the hypoxia-independent mechanisms of flow-induced shear stress in sensitizing tumors to radiation.Colon cancer cells were seeded onto glass slides pre-coated with fibronectin. A parallel-plate flow chamber system was used to impose fluid shear stress. Cell proliferation, apoptosis and colony assays were measured after shear stress and/or radiation. Cell cycle analysis and immunoblots of cell adhesion signal molecules were evaluated. The effect of shear stress was reversed by modulating integrin β1 or FAK.Shear stress of 12dyne/cm 2 for 24h, but not 3h, enhanced the radiation induced cytotoxicity to colon cancer cells. Protein expression of FAK was significantly down-regulated but not transcriptionally suppressed. By modulating integrin β1 and FAK expression, we demonstrated that shear stress enhanced tumor radiosensitivity by regulating integrin β1/FAK/Akt as well as integrin β1/FAK/cortactin pathways. Shear stress in combination with radiation might regulate integrins signaling by recruiting and activating caspases 3/8 for FAK cleavage followed by ubiquitin-mediated proteasomal degradation.Shear stress enhanced the radiation toxicity to colon cancer cells through suppression of integrin signaling and protein degradation of FAK. The results of our study provide a strong rationale for cancer treatment that combines between radiation and strategy in modulating tumor interstitial fluid flow.

Original languageEnglish
Pages (from-to)2129-2137
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number9
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Integrins
Radiation
Colonic Neoplasms
Neoplasms
Extracellular Fluid
Cortactin
Caspase 8
Radiation Tolerance
Cell Adhesion Molecules
Ubiquitin
Radio
Fibronectins
Caspase 3
Antineoplastic Agents
Proteolysis
Glass
Cell Cycle
Cell Proliferation
Apoptosis
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

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abstract = "Recent studies revealed that the interstitial fluid flow in and around tumor tissue not only played an important role in delivering anticancer agents, but also affected the microenvironment, mostly hypoxia, in modulating tumor radio-sensitivity. The current study investigated the hypoxia-independent mechanisms of flow-induced shear stress in sensitizing tumors to radiation.Colon cancer cells were seeded onto glass slides pre-coated with fibronectin. A parallel-plate flow chamber system was used to impose fluid shear stress. Cell proliferation, apoptosis and colony assays were measured after shear stress and/or radiation. Cell cycle analysis and immunoblots of cell adhesion signal molecules were evaluated. The effect of shear stress was reversed by modulating integrin β1 or FAK.Shear stress of 12dyne/cm 2 for 24h, but not 3h, enhanced the radiation induced cytotoxicity to colon cancer cells. Protein expression of FAK was significantly down-regulated but not transcriptionally suppressed. By modulating integrin β1 and FAK expression, we demonstrated that shear stress enhanced tumor radiosensitivity by regulating integrin β1/FAK/Akt as well as integrin β1/FAK/cortactin pathways. Shear stress in combination with radiation might regulate integrins signaling by recruiting and activating caspases 3/8 for FAK cleavage followed by ubiquitin-mediated proteasomal degradation.Shear stress enhanced the radiation toxicity to colon cancer cells through suppression of integrin signaling and protein degradation of FAK. The results of our study provide a strong rationale for cancer treatment that combines between radiation and strategy in modulating tumor interstitial fluid flow.",
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Radiation sensitization of tumor cells induced by shear stress : The roles of integrins and FAK. / Luo, Chi Wen; Wu, Chia-Ching; Ch'ang, Hui Ju.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1843, No. 9, 01.01.2014, p. 2129-2137.

Research output: Contribution to journalArticle

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