Involvement of adenosine A2B receptor in radiation-induced translocation of epidermal growth factor receptor and DNA damage response leading to radioresistance in human lung cancer cells

• Published in: Biochimica et biophysica acta. General subjects Vol. 1864; no. 1; p. 129457
• Main Authors: Kitabatake, Kazuki, Yoshida, Eiko, Kaji, Toshiyuki, Tsukimoto, Mitsutoshi
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.01.2020
• Subjects: Adenosine receptor; antagonists; Cancer cell; cell lines; DNA; DNA damage; DNA repair; Epidermal growth factor receptor; epidermal growth factor receptors; fluorescent antibody technique; humans; ionization; ionizing radiation; irradiation; lung neoplasms; neoplasm cells; phosphorylation; purinergic receptors; Radiation; radiation resistance; radiotherapy; Cancer cell; Adenosine receptor; DNA damage; Epidermal growth factor receptor; Radiation
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2019.129457

Adenosine receptors are involved in tumor growth, progression, and response to therapy. Among them, A2B receptor is highly expressed in various tumors. Furthermore, ionizing radiation induces translocation of epidermal growth factor receptor (EGFR), which promotes DNA repair and contributes to radioresistance. We hypothesized that A2B receptor might be involved in the translocation of EGFR. We investigated whether A2B receptor is involved in EGFR translocation and DNA damage response (γH2AX/53BP1 focus formation) of lung cancer cells by means of immunofluorescence studies. Radiosensitivity was evaluated by colony formation assay after γ-irradiation. A2B receptor was expressed at higher levels in cancer cells than in normal cells. A2B receptor antagonist treatment or A2B receptor knockdown suppressed EGFR translocation, γH2AX/53BP1 focus formation, and colony formation of lung cancer cell lines A549, calu-6 and NCI-H446, compared with a normal cell line (beas-2b). γ-Irradiation-induced phosphorylation of src and EGFR was also attenuated by suppression of A2B receptor expression. Activation of A2B receptor mediates γ-radiation-induced translocation of EGFR and phosphorylation of src and EGFR, thereby promoting recovery of irradiated lung cancer cells from DNA damage. Our results indicate that A2B receptors contribute to radiation resistance in a cancer-cell-specific manner, and may be a promising target for radiosensitizers in cancer radiotherapy. [Display omitted] •We studied an involvement of A2B receptor in radioresistance of lung cancer cells.•Inhibition of A2B receptor suppressed radiation-induced EGFR-translocation.•Inhibition of A2B receptor promoted radiosensitivity by suppression of DNA repair.•A2B receptor strongly expressed in lung cancer cells but not in normal cells.•A2B receptor may be a novel therapeutic target for radiosensitizer in cencer radiotherapy.