2. Academic Validation
  3. Downregulation of tropomyosin 2 promotes the progression of lung adenocarcinoma by regulating neutrophil infiltration through neutrophil elastase

Downregulation of tropomyosin 2 promotes the progression of lung adenocarcinoma by regulating neutrophil infiltration through neutrophil elastase

  • Cell Death Dis. 2025 Apr 8;16(1):264. doi: 10.1038/s41419-025-07531-1.
Caixiu Huang # 1,  Hao Qiu # 2,  Changting Xu 1,  Zilong Tan 3,  Mei Jin 4,  Jing Hu 1,  Zhilong Huang 5,  Yuwei Zhou 3,  Shengyou Ge 6,  Xiaoyuan Hu 7
Affiliations

Affiliations

  • 1 Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, PR China.
  • 2 The First People's Hospital of Changde City, Changde, PR China.
  • 3 Nanchang University Second Affiliated Hospital, Nanchang, PR China.
  • 4 Pingxiang People's Hospital, Pingxiang, PR China.
  • 5 Guangxi Medical College, Nanning, PR China.
  • 6 Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, PR China. shengyouge@163.com.
  • 7 Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, PR China. huxiaoyuan0821@163.com.
  • # Contributed equally.
PMID: 40199876 DOI: 10.1038/s41419-025-07531-1
Abstract

Lung adenocarcinoma (LUAD) is a common malignant tumor in the lung that seriously endangers the health of people worldwide. The neutrophil-associated inflammatory microenvironment contributes to the activation of tumor cells. In this study, we report a role of tumor-associated neutrophils (TANs) promote tumor progression of LUAD by crosstalk between neutrophils and tumor cells. Mechanistically, in co-culture with tumor cells, downregulation of TPM2 on tumor cells increases neutrophil Elastase (ELANE) levels in neutrophils regulated by p38/ MAPK signaling activation, and ELANE promotes tumor cell progression through the Hippo pathway. Furthermore, downregulation of TPM2 activates ELANE of neutrophils to facilitate ERK1/2 activation, thus enhancing IL1β and IL8 secretion for chemoattraction of more neutrophils to tumor microenvironment. The new studies identify an accomplice role for the interaction between TPM2 and ELANE in promoting LUAD progression and provide potential strategies in the prevention and/or treatment of LUAD and Other cancers.

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