2. Academic Validation
  3. Lipocalin-2 inhibits pancreatic cancer stemness via the AKT/c-Jun pathway

Lipocalin-2 inhibits pancreatic cancer stemness via the AKT/c-Jun pathway

  • Hum Cell. 2022 Sep;35(5):1475-1486. doi: 10.1007/s13577-022-00735-z.
Peipei Hao  # 1 2,  Jiamin Zhang  # 1 2,  Shu Fang 1 2,  Miaomiao Jia 1 2,  Xian Xian 2 3,  Sinan Yan 4,  Yunpeng Wang 5,  Qian Ren 1 2,  Fengming Yue 6 7,  Huixian Cui 8 9
Affiliations

Affiliations

  • 1 Department of Human Anatomy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China.
  • 2 International Cooperation Laboratory of Stem Cell Research, Shijiazhuang, Hebei, China.
  • 3 Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, Hebei, China.
  • 4 Department of Otorhinolaryngology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • 5 Department of General Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
  • 6 International Cooperation Laboratory of Stem Cell Research, Shijiazhuang, Hebei, China. yueratjp@shinshu-u.ac.jp.
  • 7 Department of Histology and Embryology, Shinshu University School of Medicine, Matsumoto, Nagano, 390-0312, Japan. yueratjp@shinshu-u.ac.jp.
  • 8 Department of Human Anatomy, Hebei Medical University, 361 East Zhongshan Road, Shijiazhuang, 050017, Hebei, China. hbmucuihx@163.com.
  • 9 International Cooperation Laboratory of Stem Cell Research, Shijiazhuang, Hebei, China. hbmucuihx@163.com.
  • # Contributed equally.
PMID: 35792978 DOI: 10.1007/s13577-022-00735-z
Abstract

Cancer Stem Cells (CSCs) are involved in Cancer recurrence and metastasis owing to their self-renewal properties and drug-resistance capacity. Lipocalin-2 (Lcn2) of the lipocalin superfamily is highly expressed in pancreatic Cancer. Nevertheless, reports on the involvement of Lcn2 in the regulation of pancreatic CSC properties are scant. This study is purposed to investigate whether Lcn2 plays a crucial role in CSC renewal and stemness maintenance in pancreatic carcinoma. Immunohistochemistry results of tumor tissue chips together with Gene Expression Omnibus Sequencing files confirmed that Lcn2 is highly expressed in pancreatic carcinoma compared with that in normal tissues. The exogenous expression of Lcn2 attenuated CSC-associated SOX2, CD44, and EpCAM expression and suppressed sarcosphere formation and tumorigenesis in the pancreatic carcinoma cell line PANC-1, which showed low expression of Lcn2. However, Lcn2 knockout in BxPC-3 cell line, which presented high Lcn2 expression, promoted CSC stemness, further enhancing sarcosphere formation and tumorigenesis. Moreover, Lcn2 was found to regulate stemness in pancreatic Cancer depending on the activation of Akt and c-Jun. Lcn2 suppresses stemness properties in pancreatic carcinoma by activating the AKT-c-Jun pathway, and thus, it may be a novel candidate to suppress the stemness of pancreatic Cancer. This study provides a new insight into disease progression.

Keywords

AKT-c-Jun pathway; Cancer biology; Cancer stem cells; Lipocalin-2; Pancreatic cancer.

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