2. Academic Validation
  3. KPNA5 Suppresses Malignant Progression of Ovarian Cancer Through Importing the PTPN4 Into the Nucleus

KPNA5 Suppresses Malignant Progression of Ovarian Cancer Through Importing the PTPN4 Into the Nucleus

  • Cancer Med. 2025 Apr;14(7):e70731. doi: 10.1002/cam4.70731.
Yanming Hu 1,  Jing Zhou 2,  Xinru Ling 3,  Kun Zhao 4,  Peng Huang 1,  Max Gao 5,  Xiaoqing Li 1,  Ming Sun 1,  Yanfen Zou 6,  Guannan Feng 3
Affiliations

Affiliations

  • 1 Suzhou Cancer Center Core Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Suzhou, China.
  • 2 Department of Oncology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, China.
  • 3 Department of Obstetrics and Gynecology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Suzhou, China.
  • 4 Department of Oncology, Huaian Hospital of Huaian City, Huaian, Jiangsu, China.
  • 5 Department of Computer Science and Engineering, University of California, Davis, California, USA.
  • 6 Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
PMID: 40145330 DOI: 10.1002/cam4.70731
Abstract

Background: Abnormal protein localization due to disrupted nucleoplasmic transport is common in tumor cells, but its mechanisms are not well understood. Nuclear pore complexes and nuclear transporter proteins are crucial for protein transport between the nucleus and cytoplasm. Evidence increasingly shows that abnormal expression of karyopherin family proteins disrupts protein translocation, affecting processes like cell differentiation, proliferation, Apoptosis, and transcriptional regulation. However, their functions and roles in ovarian Cancer remain unclear.

Methods: The expression level of KPNA5 in ovarian Cancer tissues and cells was detected by IHC, Western blot, and qPCR. CCK-8 and colony formation assays were used to assess cell proliferation ability. Transwell assay was conducted to determine cell migration and invasion capacity. A xenograft model was used to assess the effect of KPNA5 on tumor growth in vivo.

Results: KPNA5 expression is downregulated in ovarian Cancer (OC) tissues. Low KPNA5 levels were associated with poor survival in OC patients, validated by an OC tissue sample cohort. Overexpression of KPNA5 significantly suppressed OC cell proliferation, tumor growth, and invasion in both in vitro and in vivo studies. Mechanistically, KPNA5 recognizes nuclear localization signals (NLSs) in PTPN4, mediating its nuclear transport and inhibiting STAT3 phosphorylation and its downstream signaling pathway. Similarly, PTPN4 overexpression reduced OC cell viability and invasion, also suppressing STAT3 phosphorylation.

Conclusions: Our findings identify KPNA5 as a tumor suppressor in OC, presenting a potential therapeutic target for OC treatment.

Keywords

KPNA5; PTPN4; STAT3; ovarian cancer; tumor suppressor.

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