2. Academic Validation
  3. HK2 promotes migration and invasion of intrahepatic cholangiocarcinoma via enhancing cancer stem-like cells' resistance to anoikis

HK2 promotes migration and invasion of intrahepatic cholangiocarcinoma via enhancing cancer stem-like cells' resistance to anoikis

  • Cell Signal. 2024 Mar 5:118:111126. doi: 10.1016/j.cellsig.2024.111126.
Xiaojing Du 1,  Zhuoran Qi 2,  Yunjia Jiao 3,  Wenzhi Wu 4,  Qingke Huang 4,  Xuecheng Sun 4,  Sunkuan Hu 5
Affiliations

Affiliations

  • 1 Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
  • 2 Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 3 Clinical Laboratory, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Shanghai 201199, China.
  • 4 Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 5 Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.. Electronic address: [email protected].
PMID: 38453126 DOI: 10.1016/j.cellsig.2024.111126
Abstract

Cancer stem-like cells (CSLCs) and anoikis resistance play crucial roles in the metastasis of cancers. However, it remains unclear whether CSLCs are related to anoikis resistance in intrahepatic cholangiocarcinoma (ICC). Here we identified a group of stemness-related anoikis genes (SRAGs) via bioinformatic analysis of public data. Accordingly, a novel anoikis-related classification was established and it divided ICC into C1 and C2 type. Different type ICC displayed distinct prognosis, molecular as well immune characteristics. Furthermore, we found one key SRAGs via several machine learning algorithms. HK2 was up-regulated in tumor-repopulating cells (TRCs) of ICC, a kind of CSLCs with a potent resistance to anoikis. Its up-regulation may be caused by the activation of mTORC1 signaling in ICC-TRCs. And inhibition of HK2 significantly increased anoikis and decreased migration as well invasion in ICC-TRCs. Our studies provide an insight into the molecular mechanism underlying the resistance of ICC-TRCs to anoikis and enhance the evidences for targeting HK2 in ICC.

Keywords

Anoikis; Cancer stem-like cells; HK2; Intrahepatic cholangiocarcinoma; Invasion and migration.

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