# Targeting understudied kinases in cancer cell plasticity and drug resistance

> **NIH NIH R03** · UNIVERSITY OF WASHINGTON · 2020 · $155,500

## Abstract

Project Summary
Metastasis is responsible for 90% of cancer-related deaths and novel drugs that target this
disease stage are urgently needed. Metastatic cancer cells exploit developmental pathways to
acquire a mesenchymal stem cell-like state. This epithelial-mesenchymal transition (EMT)
enhances cancer cell motility, invasion and survival. Inhibition of EMT, in turn, can block
metastasis and, strikingly, can sensitize cancer cells to chemotherapy. A critical goal of cancer
drug discovery, therefore, is to identify druggable proteins that promote the EMT. In a detailed
pharmacoproteomics study of hepatocellular carcinoma (HCC), we demonstrated that protein
kinases are critical drivers of EMT and drug resistance. Remarkably, our study predicted 71
kinases to promote EMT, among them six understudied IDG targets. We will evaluate the
translational potential of these six IDG kinases, i.e. NUAK2, CAMK1D, STK17A, STK17B,
STK32B and CDK10, by scrutinizing their function in EMT and drug resistance. We will use
targeted gene disruption with CRISPR/Cas9 to knock-out (KO) these kinases in mesenchymal
HCC cell lines and ectopically express them in epithelial HCC lines. Impact on EMT state and
drug resistance will be tested (1) by qPCR and western blot analysis of 15 reliable EMT
markers, (2) in a robust trans-well invasion assay, and (3) a small-scale drug screen.
Combining efficient KO with these orthogonal assays will ensure unambiguous specification of
kinase roles in HCC cell EMT and drug response.

## Key facts

- **NIH application ID:** 10045760
- **Project number:** 1R03TR003308-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Martin Golkowski
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $155,500
- **Award type:** 1
- **Project period:** 2020-09-08 → 2022-09-07

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045760

## Citation

> US National Institutes of Health, RePORTER application 10045760, Targeting understudied kinases in cancer cell plasticity and drug resistance (1R03TR003308-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10045760. Licensed CC0.

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