2. Academic Validation
  3. KIAA1217 Promotes Epithelial-Mesenchymal Transition and Hepatocellular Carcinoma Metastasis by Interacting with and Activating STAT3

KIAA1217 Promotes Epithelial-Mesenchymal Transition and Hepatocellular Carcinoma Metastasis by Interacting with and Activating STAT3

  • Int J Mol Sci. 2021 Dec 22;23(1):104. doi: 10.3390/ijms23010104.
Yanhong Wang 1 2,  Na Li 1,  Yanping Zheng 1,  Anqing Wang 1,  Chunlei Yu 1,  Zhenbo Song 2,  Shuyue Wang 2,  Ying Sun 1,  Lihua Zheng 2,  Guannan Wang 2,  Lei Liu 2,  Jingwen Yi 2,  Yanxin Huang 1,  Muqing Zhang 3,  Yongli Bao 1,  Luguo Sun 1
Affiliations

Affiliations

  • 1 National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
  • 2 NMPA Key Laboratory for Quality of Cell and Gene Therapy Medicinal Products, Northeast Normal University, Changchun 130024, China.
  • 3 School of Molecular and Cellular Biology, University of Illinois Urbana Champaign, Urbana, IL 61801, USA.
PMID: 35008530 DOI: 10.3390/ijms23010104
Abstract

The survival and prognosis of hepatocellular carcinoma (HCC) are poor, mainly due to metastasis. Therefore, insights into the molecular mechanisms underlying HCC invasion and metastasis are urgently needed to develop a more effective antimetastatic therapy. Here, we report that KIAA1217, a functionally unknown macromolecular protein, plays a crucial role in HCC metastasis. KIAA1217 expression was frequently upregulated in HCC cell lines and tissues, and high KIAA1217 expression was closely associated with shorter survival of patients with HCC. Overexpression and knockdown experiments revealed that KIAA1217 significantly promoted cell migration and invasion by inducing epithelial-mesenchymal transition (EMT) in vitro. Consistently, HCC cells overexpressing KIAA1217 exhibited markedly enhanced lung metastasis in vivo. Mechanistically, KIAA1217 enhanced EMT and accordingly promoted HCC metastasis by interacting with and activating JAK1/2 and STAT3. Interestingly, KIAA1217-activated p-STAT3 was retained in the cytoplasm instead of translocating into the nucleus, where p-STAT3 subsequently activated the Notch and Wnt/β-catenin pathways to facilitate EMT induction and HCC metastasis. Collectively, KIAA1217 may function as an adaptor protein or scaffold protein in the cytoplasm and coordinate multiple pathways to promote EMT-induced HCC metastasis, indicating its potential as a therapeutic target for curbing HCC metastasis.

Keywords

KIAA1217; STAT3; epithelial-mesenchymal transition; hepatocellular carcinoma; metastasis.

Figures
Products