Related Experiment Video

Updated: Jul 2, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

19.8K

Enhanced SLC35B2/SAV1 sulfation axis promotes tumor growth by inhibiting Hippo signaling in HCC

Bo He1, Zhao Huang1, Siyuan Qin1

  • 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.

Hepatology (Baltimore, Md.)
|February 20, 2024
PubMed
Abstract

Insights

Protein tyrosine sulfation (PTS) of SAV1, driven by SLC35B2, inactivates Hippo signaling and promotes hepatocellular carcinoma (HCC) growth. This axis offers a potential therapeutic target for HCC progression.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Protein tyrosine sulfation (PTS) is a critical posttranslational modification with poorly understood roles in cancer.
  • Hepatocellular carcinoma (HCC) progression involves complex regulatory pathways.

Purpose of the Study:

  • To investigate the role and mechanisms of PTS in HCC progression.
  • To identify novel PTS substrates and their functions in HCC.

Main Methods:

  • Mass spectrometry and bioinformatics analysis to identify PTS substrates.
  • Investigated the regulation of SLC35B2 and its impact on SAV1 sulfation.
  • Assessed the effect of SAV1 sulfation on Hippo signaling pathway activity in vitro and in vivo.

Main Results:

  • SAV1 identified as a novel PTS substrate in HCC.
  • Oxidative stress increases SLC35B2 transcription, leading to enhanced SAV1 sulfation.
  • SAV1 sulfation disrupts the SAV1-MST1 complex, inactivating Hippo signaling and promoting HCC growth.
  • SLC35B2 is a Hippo pathway target, forming a positive feedback loop that exacerbates HCC progression under oxidative stress.

Conclusions:

  • A novel regulatory axis involving SLC35B2/SAV1 sulfation in response to oxidative stress was revealed.
  • This pathway plays a significant role in facilitating HCC progression.
  • The SLC35B2/SAV1 sulfation axis represents a potential therapeutic target for HCC.

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