AMIGO2 attenuates innate cisplatin sensitivity by suppression of GSDME‐conferred pyroptosis in non‐small cell lung cancer

Non‐small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer. Cisplatin is commonly used in the treatment of many malignant tumours including NSCLC. The innate drug sensitivity greatly affects the clinical efficacy of cisplatin‐based chemotherapy. As a plasma membrane adhesion mo...

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Bibliographic Details
Published in:Journal of cellular and molecular medicine 2023-08, Vol.27 (16), p.2412-2423
Main Authors: Chen, Lian‐kuai, Lin, Shu‐ping, Xie, Yong‐huan, Tan, Xiang‐peng, Xiong, Ben‐han, Zeng, Xiang‐feng, Zhu, Cai‐rong, Cao, Shao‐yi, Ye, Xiao‐yan, Liu, Hong‐jiao, Wu, Xiao‐ping
Format: Article
Language:English
Subjects:
AKT protein
AMIGO2
Antibodies
Apoptosis
Axonogenesis
Cancer therapies
Caspase-3
Caspase-8
Caspase-9
Cell adhesion & migration
Cell culture
Chemotherapy
Cisplatin
Dehydrogenases
GSDME
innate cisplatin sensitivity
Lung cancer
Metastasis
Mortality
Non-small cell lung carcinoma
non‐small cell lung cancer
Original
Proteins
Pyroptosis
Small cell lung carcinoma
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Summary:Non‐small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer. Cisplatin is commonly used in the treatment of many malignant tumours including NSCLC. The innate drug sensitivity greatly affects the clinical efficacy of cisplatin‐based chemotherapy. As a plasma membrane adhesion molecule, amphoterin‐induced gene and ORF‐2 (AMIGO2) initially identified as a neurite outgrowth factor has been recently found to play a crucial role in cancer occurrence and progression. However, it is still unclear whether AMIGO2 is involved in innate cisplatin sensitivity. In the present study, we provided the in vitro and in vivo evidences indicating that the alteration of AMIGO2 expression triggered changes of innate cisplatin sensitivity as well as cisplatin‐induced pyroptosis in NSCLC. Further results revealed that AMIGO2 might inhibit cisplatin‐induced activation of (caspase‐8 and caspase‐9)/caspase‐3 via stimulating PDK1/Akt (T308) signalling axis, resulting in suppression of GSDME cleavage and the subsequent cell pyroptosis, thereby decreasing the sensitivity of NSCLC cells to cisplatin treatment. The results provided a new insight that AMIGO2 regulated the innate cisplatin sensitivity of NSCLC through GSDME‐mediated pyroptosis.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.17827