J Cancer 2019; 10(17):4085-4095. doi:10.7150/jca.30012 This issue

Research Paper

Regulation of response to radiotherapy by β-arrestin1 in Non-small cell lung cancer

Liguang Wang1,2*, Kai Wang3*, Wei Dong4, Hongchang Shen2✉, Jiajun Du1,4✉

1. Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, P.R. China
2. Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, P.R. China
3. Department of Healthcare Respiratory, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, P.R. China
4. Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, P.R. China
*These authors contributed equally to this work.

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Citation:
Wang L, Wang K, Dong W, Shen H, Du J. Regulation of response to radiotherapy by β-arrestin1 in Non-small cell lung cancer. J Cancer 2019; 10(17):4085-4095. doi:10.7150/jca.30012. Available from https://www.jcancer.org/v10p4085.htm

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Abstract

β-arrestin1 serves as scaffold proteins participating in multiple signaling pathways. However, there were few researches focusing on the impact of β-arrestin1 on DNA damage response (DDR). Non-small cell lung cancer cell (NSCLC) lines were transfected with β-arrestin1 plasmids or siRNA and received radiation treatment. MTT and colony formation assay were performed to assess the proliferation and viability of tumor cells. Flow cytometry was used to evaluate the impact of β-arrestin1 on radiation-induced apoptosis. Western blotting was applied to detect protein expression in apoptosis, DDR, ERK and NF-kB pathways. We used qRT-PCR to test ATR, H2AX, β-arrestin1 mRNA level in cancer tissues compared with para-carcinoma tissues. Co-IP was performed to evaluate the interaction between β-arrestin1 and ATR or H2AX. Comet assay was used to detect DNA damage. β-arrestin1 mRNA level co-related with ATR and H2AX levels in cancer tissues, and β-arrestin1 bound to ATR and H2AX directly or indirectly. Overexpression of β-arrestin1 enhanced the DNA damage response pathway activation and increase DNA damage and apoptosis. Interestingly, suppression of β-arrestin1 inhibited cell proliferation and attenuated ERK and NF-kB pathways activation induced by radiation. Overexpression of β-arrestin1 enhances DDR pathway activation induced by radiation, as well as downstream apoptosis, and depletion of β-arrestin1 inhibits DDR pathway. Meanwhile β-arrestin1 regulates cell proliferation by suppression of ERK and NF-kB pathways. Manipulation of β-arrestin1 status modulates radiosensitivity for NSCLC.

Keywords: β-arrestin1, NSCLC, Radiotherapy, DDR, Apoptosis