Overexpression of JAML in colorectal cancer cells predicts higher radiosensitivity by inactivating ATR pathway

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Background Junctional adhesion molecule–like protein (JAML) is highly expressed in cancer tissues of patients with colorectal cancer (CRC) and promotes cancer proliferation. However, the relationship between JAML expression and radiosensitivity of CRC remains unclear. Methods Stable CRC cell lines with knocked down or overexpressed JAML were used to evaluate the effects of irradiation on cell viability and cell proliferation using Cell Counting Kit-8 (CCK8) and cell clone formation assay, respectively. Cellular immunofluorescence, flow cytometry, and western blotting were used to determine the mechanism. Tumor-bearing nude mouse models were established to verify the relationships between the expression of JAML and the radiosensitivity of CRC. Results The results of CCK8 and cell clone formation assay showed that the viability and proliferation of CRC cells with JAML overexpression were significantly inhibited after exposure to irradiation compared with those of CRC cells with low expression of JAML. DNA damage and cell apoptosis were significantly increased in the JAML-overexpression group compared with the JAML-low-expression group after exposure to irradiation. The phosphorylation of the ataxia telangiectasia and Rad3-related protein (ATR)-checkpoint kinase 1 (CHK1)-mediated DNA damage repair pathway was inhibited in the JAML-overexpression group compared with the JAML-low-expression CRC cells after irradiation. Similar results were observed in CRC xenografts in vivo . Conclusions CRC cells with JAML overexpression are more sensitive to radiotherapy of X-rays because of the decreased phosphorylation of the ATR-CHK1-mediated DNA damage repair pathway. The expression of JAML in CRC cells could be used as a predictive biomarker of radiosensitivity in patients with CRC.

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