# PIPKIgammai5 in the Control of HNSCC Progression

> **NIH NIH R01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $368,719

## Abstract

Project Summary
Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key lipid-signaling molecule that regulates a vast array of
biological activities. However, the function of PIP2-regulated signaling in mammalian cell-fate decision and
tumorigenesis has received less attention. Research from our laboratory indicates that an endosome-localized
PIP2 producing enzyme, type I gamma phosphatidylinositol phosphate kinase i5 (PIPKIγi5), is crucial for the
regulation of Epidermal Growth Factor Receptor (EGFR) and Hippo signaling, two essential signaling pathways
in the control of cell proliferation and Cancer Stem Cell (CSC) regeneration. The dysregulation of EGFR or
Hippo signaling has been found in many types of cancers including head and neck squamous cell carcinoma
(HNSCC). Here is the current hypothesis: By interacting with the small GTPase Rab7a, PIPKIγi5 modulates
EGFR endosomal trafficking and degradation; By interacting with the E3 ubiquitin ligase Neuronal precursor
cell-expressed developmentally downregulated 4 (NEDD4), PIPKIγi5 controls the stability of Hippo pathway
core components WW45 and LATS2; Via modulating the EGFR and Hippo signaling, PIPKIγi5 controls
HNSCC CSC regeneration, tumorigenesis, and metastasis. Aim 1 will characterize the PIPKIγi5-Rab7a
interaction and determine whether this interaction controls EGFR signaling by modulating endosome
maturation. Aim 1 will also demonstrate whether PIPKIγi5 controls the Hippo core components WW45/LATS2
ubiquitination and degradation by associating with NEDD4. In Aim 2, both in vitro cell line models and in vivo
xenograft mouse models will be used to determine the effects of PIPKIγi5 on HNSCC CSC self-renewal and
metastasis. Furthermore, Aim 2 will further validate the function of PIPKIγi5 in HNSCC tumorigenesis by using
PIPKIγi5-knockout mouse models. The successful completion of this application will reveal a novel PIP2-
regulated pathway that controls HNSCC progression by modulating EGFR and Hippo signaling.

## Key facts

- **NIH application ID:** 9945011
- **Project number:** 1R01DE029496-01
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Yue Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,719
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9945011

## Citation

> US National Institutes of Health, RePORTER application 9945011, PIPKIgammai5 in the Control of HNSCC Progression (1R01DE029496-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9945011. Licensed CC0.

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