Surgical Management of Non-Small Cell Lung Cancer Invading the Fissure: Less Is More?

Cisplatin (CDDP)-based chemotherapy is commonly used to treat advanced non-small cell lung cancer (NSCLC). However, the e cacy is limited by the development of drug resistance. Tripartite motif (TRIM) proteins typically have E3 ubiquitin ligase activities and modulate protein stability. In the present study, we screened for chemosensitivity-regulating TRIM proteins using CDDP-resistant NSCLC cell lines. We show that TRIM17 is upregulated in CDDP-resistant NSCLC cells and tumors compared to CDDP-sensitive counterparts. NSCLC patients with high TRIM17 expression in tumors have shorter progression-free survival than those with low TRIM17 expression after CDDP chemotherapy. Knockdown of TRIM17 increases the sensitivity of NSCLC cells to CDDP both in vitro and in vivo. In contrast, overexpression of TRIM17 promotes CDDP resistance in NSCLC cells. TRIM17-mediated CDDP resistance is associated with attenuation of reactive oxygen species (ROS) production and DNA damage. Mechanistically, TRIM17 interacts with RBM38 and promotes K48-linked ubiquitination and degradation of RBM38. TRIM17induced CDDP resistance is remarkably reversed by RBM38. Additionally, RBM38 enhances CDDPinduced production of ROS. In conclusion, TRIM17 upregulation drives CDDP resistance in NSCLC largely by promoting RBM38 ubiquitination and degradation. Targeting TRIM17 may represent a promising strategy for improving CDDP-based chemotherapy in NSCLC.

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Lappenübergreifendes NSCLC – maximale vs. parenchymschonende Resektion

2021

Zentralbl Chir

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Surgical Management of Non-Small Cell Lung Cancer Invading the Fissure: Less Is More?

Cited by 6 publications

References 14 publications

Adjacent lobe invasion of T2 tumor in non-small cell lung cancer has T3 disease-like survival fissure invasion: T2 or T3?

Adjacent lobe invasion of T2 tumor in non-small cell lung cancer has T3 disease-like survival fissure invasion: T2 or T3?

TRIM17-mediated ubiquitination and degradation of RBM38 promotes cisplatin resistance in non-small cell lung cancer

Lappenübergreifendes NSCLC – maximale vs. parenchymschonende Resektion

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