# Identifying novel effectors of oncogenic Kras in pancreatic cells via proximity labelling

> **NIH NIH F30** · STATE UNIVERSITY NEW YORK STONY BROOK · 2020 · $50,520

## Abstract

Abstract
48,960 new cases of pancreatic cancer were predicted for 2015 and despite extensive treatment options, the 5
year relative survival rate has consistently remained below 8% for the past 40 years. Current treatments are non-
targeted agents with inherent side effects and only prolong survival on the order of months. Kras is mutated in
over 90% of pancreatic adenocarcinoma (PDAC), the most common type of pancreatic cancer. Under normal
conditions, Kras is a tightly regulated signaling protein that can toggle between active and inactive states to
control cell proliferation. Mutated Kras (G12D) predominantly remains active, thus, constitutively promoting
proliferation and tumorigenesis. Studies that target downstream pathways of Kras, Raf/ERK and PI3K/AKT,
have had some preclinical success but minimal clinical impact on pancreatic cancer. Therefore, it remains
possible that other undiscovered protein-protein interactions exist, including transient ones. This study aims to
identify such interactions via cutting edge proteomics technique, BioID (a promiscuous biotin ligase). Firstly,
BioID fusions to wild type and mutant Kras will be expressed in mouse tumor cells and human pancreas cell
lines to differentially label local proteins, and thus identify context specific interactors of Kras. The relative
amounts of proteins will be measured using mass spectrometry and western blot analysis. Preliminary data in
murine cells reveal that Rab42 is a major Kras effector. Secondly, depletion experiments of this protein of interest
will be performed to study the role of Rab42 in proliferation, transformative potential, EGF dependency,
tumorigenesis, and invasive potential in vitro. The role of Rab42 in tumor initiation and engraftment will be
determined in vivo with orthotopically grafted organoid (OGO) mouse model. This proposed study will identify
mutant specific Kras effectors and hopefully lead future studies to novel therapeutic targets for mutant Kras-
driven PDAC. Knowledge that comes out of this study may also shed light on other Kras mutant cancers such
as lung and colon adenocarcinoma.

## Key facts

- **NIH application ID:** 9837420
- **Project number:** 5F30CA213883-04
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Derek Kingman Cheng
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-01-15 → 2021-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837420

## Citation

> US National Institutes of Health, RePORTER application 9837420, Identifying novel effectors of oncogenic Kras in pancreatic cells via proximity labelling (5F30CA213883-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9837420. Licensed CC0.

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