Liver cancer: WISP3 suppresses hepatocellular carcinoma progression by negative regulation of β‐catenin/TCF/LEF signalling

Abstract

Objectives: Wnt1-inducible signalling pathway protein 3 (WISP3/CCN6) belongs to the CCN (CYR61/CTGF/NOV) family of proteins, dysregulation of this family contributed to the tumorigenicity of various tumours. In this study, we need to explore its role in hepatocellular carcinoma that remains largely elusive. Materials and Methods:The expression of WISP3/CCN6 was analysed by qRT-PCR and Western blotting. Effects of WISP3 on proliferation and metastasis of HCC cells were examined, respectively, by MTT assay and Boyden Chamber. Roles of WISP3 on HCC tumour growth and metastatic ability in vivo were detected in nude mice.Related mechanism study was confirmed by immunofluorescence and Western blotting. Results: The expression of WISP3 was significantly downregulated in HCC clinical samples and cell lines, and reversely correlated with the tumour size. Forced expression of WISP3 in HCC cells significantly suppressed cell growth and migration in vitro as well as tumour growth and metastatic seeding in vivo. In contrast, downregulation of WISP3 accelerated cell proliferation and migration, and promoted in vivo S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article.

CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment

“…CCN5 is a tumor suppressor, which restored ER-α expression at the transcription level via integrins-α6β1/Akt/FOXO3a signaling activation in breast cancer ( Sarkar et al, 2017 ). CCN6 is also acts as a tumor suppressor in HCC by negative regulation of β-catenin/TCF/LEF signaling ( Gao et al, 2019 ). Because of the four functional domains of CCN proteins, CCNs mediate tumor progression primarily through binding and interacting with well-known receptors, including integrins, HSPGs, IGFs and LRPs relating the signaling pathways such as Wnts, TGF-β, and Notch signaling et al ( Li et al, 2015 ).…”

CXCL14 facilitates the growth and metastasis of ovarian carcinoma cells via activation of the Wnt/β-catenin signaling pathway

“…The key molecular events in Wnt signaling are nuclear β-catenin accumulation and β-catenin/TCF4 complex transcriptional activity [ 28 ]. Nuclear β-catenin binds to members of the TCF/LEF family of transcription factors, including Twist and Snail1/2, to trigger EMT [ 29 , 30 ]. Although β-catenin serves as a downstream effector in CXCL14-induced OC cell growth and invasion, it deserves further exploration of the complex interaction of β-catenin and CXCL14.…”

CXCL14 Facilitates the Growth and Metastasis of Ovarian Carcinoma Cells via Activation of the Wnt/β-catenin Signaling Pathway

“…The key molecular events in Wnt signaling are nuclear β-catenin accumulation and β-catenin/TCF4 complex transcriptional activity [27]. Nuclear β-catenin binds to members of the TCF/LEF family of transcription factors, including Twist and Snail1/2, to trigger EMT [28,29]. Although β-catenin serves as a downstream effector in CXCL14-induced OC cell growth and invasion, it deserves further exploration of the complex interaction of β-catenin and CXCL14.…”