2. Academic Validation
  3. BUB1b impairs chemotherapy sensitivity via resistance to ferroptosis in lung adenocarcinoma

BUB1b impairs chemotherapy sensitivity via resistance to ferroptosis in lung adenocarcinoma

  • Cell Death Dis. 2024 Jul 23;15(7):525. doi: 10.1038/s41419-024-06914-0.
Yanguang Ding # 1 2 3,  Jian Gao # 4,  Jun Chen # 1 2,  Jinmei Ren 5,  Jiahao Jiang 4,  Zhiqiang Zhang 3,  Xin Tong 6 7,  Jun Zhao 8 9
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.
  • 3 Department of Thoracic Surgery, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China.
  • 4 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 5 Department of Pharmacy, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China.
  • 6 Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. txin@suda.edu.cn.
  • 7 Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. txin@suda.edu.cn.
  • 8 Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. zhaojia0327@126.com.
  • 9 Institute of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. zhaojia0327@126.com.
  • # Contributed equally.
PMID: 39043653 DOI: 10.1038/s41419-024-06914-0
Abstract

BUB1 mitotic checkpoint serine/threonine kinase B (BUB1b) has been unequivocally identified as an oncogene in various cancers. However, the potential mechanism by which BUB1b orchestrates the progression of lung adenocarcinoma (LUAD) remains unclear. Here we found that both the transcript and protein levels of BUB1b were dramatically upregulated in tumor tissues and contributed to the dismal prognosis of LUAD patients. Moreover, gain- and loss-of-function assays, conducted both in vitro and in vivo, confirmed that BUB1b enhanced the viability of LUAD cells. Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to Ferroptosis and chemotherapy. In BALB/c nude mice bearing subcutaneous tumors that overexpress BUB1b, a combined strategy of ML385 targeting and chemotherapy achieved synergistic effects, inhibiting tumor growth and obviously improving survival. Taken together our study uncovered the underlying mechanism by which BUB1b promotes the progression of LUAD and proposed a novel strategy to enhance the efficacy of chemotherapy.

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