# Deciphering cross-talk of signaling pathways in control of hepatocellular carcinogenesis

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $39,282

## Abstract

Project Summary
Recent studies have shown surprising tumor-suppressive roles for classically pro-oncogenic
proteins in the initiation and progression of hepatocellular carcinoma (HCC). These findings may
begin to explain why oncoprotein-targeting therapeutics have had little effect clinically, so
elucidation of the mechanisms behind these surprising activities will be needed to develop more
effective therapeutic strategies. Among these “paradoxical tumor suppressors” are the
phosphatase Shp2, which is required for full Ras/Erk signaling activation, and the kinase Ikkβ,
which is needed for activation of pro-inflammatory and anti-apoptotic NF-B signaling. The
objectives of this research are to elucidate the functional interactions of Shp2-dependent
signaling and Ikkβ-dependent NF-B activities in the initiation and progression of HCC, and to
identify the molecules that drive HCC in the absence of these usually pro-oncogenic pathways.
By integrating pathological characterization and molecular analyses, this model will uncover
tissue- and cellular-level pathology and signaling changes that drive HCC when major pro-
oncogenic pathways such as Ras/Erk and NF-B are disrupted. The results of this project will
provide new understanding of the complex interactions between the usually pro-oncogenic
signaling pathways that have been shown to suppress hepatocarcinogenesis in certain
contexts, and may help identify mechanisms of relapse after targeted therapies.

## Key facts

- **NIH application ID:** 9842269
- **Project number:** 5F31CA228420-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Kaisa Leigh Hanley
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,282
- **Award type:** 5
- **Project period:** 2018-12-07 → 2020-12-06

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842269

## Citation

> US National Institutes of Health, RePORTER application 9842269, Deciphering cross-talk of signaling pathways in control of hepatocellular carcinogenesis (5F31CA228420-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9842269. Licensed CC0.

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