Auner Lab


Dr Holger Auner

  • CRUK Advanced Clinician Scientist
  • Clinical Reader in Molecular Haemato-Oncology

+44 (0)20 3313 4017

Areas of research

Proteotoxic stress and metabolism

Myeloma cells are characterised by a unique sensitivity to inhibitors of the proteasome, which is responsible for the controlled degradation of most cellular proteins that have become damaged or are otherwise unwanted. Nevertheless, resistance to proteasome inhibitors occurs in essentially all patients to varying degrees. Accumulation of misfolded proteins in the endoplasmic reticulum (ER), which triggers proteotoxic ‘ER stress’, is widely believed to be the main mechanism of action of proteasome inhibitors. However, data from our lab and other research groups suggest complex interactions between proteasomal protein degradation and multiple metabolic processes. Our aim is to find metabolic and proteostatic vulnerabilities that we can exploit therapeutically.

Tissue biophysics in myeloma biology

Several important aspects of cancer cell biology are influenced by mechanical cues from the surrounding tissue. In particular, mechanical interactions and matrix remodelling have been shown to govern cancer cell metabolism. Tissue stiffness also impacts on normal haematopoiesis, and mechanical cues are known to modulate therapeutic responses. Moreover, we have shown that proteostasis-targeting drugs can alter tissue physical properties. We aim to understand how tissue stiffness and nutrient availability act together to rewire metabolic networks and regulate drug responses in myeloma.


BibTex format

author = {Parzych, K and Saavedra, Garcia P and Valbuena, G and Alsadah, HAH and Robinson, M and Penfold, L and Kuzeva, D and Ruiz, Tellez A and Loaiza, S and Holzmann, V and Caputo, V and Johnson, DC and Kaiser, MF and Karadimitris, A and Lam, E and Chevet, E and Feldhahn, N and Keun, H and Auner, H},
doi = {10.1038/s41388-018-0651-z},
journal = {Oncogene},
pages = {3216--3231},
title = {The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation},
url = {},
volume = {38},
year = {2019}

RIS format (EndNote, RefMan)

AB - VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. Its key role in governing protein homoeostasis has made VCP/p97 an appealing anticancer drug target. Here, we provide evidence that VCP/p97 acts as a regulator of cellular metabolism. We found that VCP/p97 was tied to multiple metabolic processes on the gene expression level in a diverse range of cancer cell lines and in patient-derived multiple myeloma cells. Cellular VCP/p97 dependency to maintain proteostasis was increased under conditions of glucose and glutamine limitation in a range of cancer cell lines from different tissues. Moreover, glutamine depletion led to increased VCP/p97 expression, whereas VCP/p97 inhibition perturbed metabolic processes and intracellular amino acid turnover. GCN2, an amino acid-sensing kinase, attenuated stress signalling and cell death triggered by VCP/p97 inhibition and nutrient shortages and modulated ERK activation, autophagy, and glycolytic metabolite turnover. Together, our data point to an interconnected role of VCP/p97 and GCN2 in maintaining cancer cell metabolic and protein homoeostasis.
AU - Parzych,K
AU - Saavedra,Garcia P
AU - Valbuena,G
AU - Alsadah,HAH
AU - Robinson,M
AU - Penfold,L
AU - Kuzeva,D
AU - Ruiz,Tellez A
AU - Loaiza,S
AU - Holzmann,V
AU - Caputo,V
AU - Johnson,DC
AU - Kaiser,MF
AU - Karadimitris,A
AU - Lam,E
AU - Chevet,E
AU - Feldhahn,N
AU - Keun,H
AU - Auner,H
DO - 10.1038/s41388-018-0651-z
EP - 3231
PY - 2019///
SN - 0950-9232
SP - 3216
TI - The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation
T2 - Oncogene
UR -
UR -
VL - 38
ER -