Our overall goal is to define how age and redox-related changes in cancer support the metastatic dissemination of tumour cells.
Lung cancer is the deadliest cancer worldwide, primarily because it is often diagnosed late, when metastases have already formed. Importantly, the risk of developing a metastatic disease is two-fold higher in cancer patients above 60 years old compared to younger patients, independently of tumor grade. Efforts to identify metastasis driver mutations have been largely unsuccessful. Instead, many studies show that cancer cells metastasize by adapting to oxidative stress and rewiring metabolic pathways. During metastatic dissemination, cancer cells are exposed to heterogenous microenvironments and stresses, including oxidative stress
To understand how oxidative stress or age shape the cross-talk between cancer cells and the metastatic niche to support their dissemination, our research employs in vitro and in vivo CRISPR/Cas9 screens, single cell sequencing and metabolomics.
Our research involves several mouse models of lung cancer and metastasis.
We also use a wide range of cellular and molecular biology methods such as cancer cell lines, reporter cell lines, biosensors, ChIP, qPCR, WB, IF/IHC, microscopy, migration and invasion assays, among many others.
Our lab, together with Sayin lab (SCCR, GU) has developed lentiviral-CRISPR/Cas9 strategies to inactivate any gene-of-interest at tumor onset or later during tumor progression and metastasis.
Current group members
Clotilde Wiel, PhD, Principal investigator (Junior PI)
Dorota Raj, PhD, Postdoc
- KRAS Mutations Impact Clinical Outcome in Metastatic Non-Small Cell Lung Cancer.
Eklund EA, Wiel C, Fagman H, Akyürek LM, Raghavan S, Nyman J, Hallqvist A, Sayin VI. (2022). Cancers (Basel), 14, 2063
- Mitochondria-Targeted Antioxidants MitoQ and MitoTEMPO Do Not Influence BRAF- Driven Malignant Melanoma and KRAS-Driven Lung Cancer Progression in Mice.
Le Gal K*, Wiel C*, Ibrahim MX, Henricsson M, Sayin VI, Bergo MO (2021) Antioxidants 10(2):163. *co-first
- Targeting RAS‐converting enzyme 1 overcomes senescence and improves progeria‐like phenotypes of ZMPSTE24 deficiency.
Yao H, Chen X, Kashif M, Wang T, Ibrahim MX, Tüksammel E, Revêchon G, Eriksson M, Wiel C* Bergo MO# (2020) Aging Cell 19: e13200 *co-corresponding
- BACH1 stabilization by antioxidants stimulates lung cancer metastasis.
Wiel C, Le Gal K, Ibrahim MX, Jahangir CA, Kashif M, Yao H, Ziegler D V., Xu X, Ghosh T, Mondal T, et al. (2019) Cell. 178: 330–345.
- The JAK1/2 inhibitor ruxolitinib delays premature aging phenotypes.
Griveau A*, Wiel C*, Ziegler DV, Bergo MO, Bernard D (2020) Aging Cell. 19: e13122. *co-first
- Antioxidants can increase melanoma metastasis in mice.
Le Gal K, Ibrahim MX, Wiel C, Sayin VI, Akula MK, Karlsson C, Dalin MG, Akyurek LM, Lindahl P, Nilsson J, et al. (2015) Sci Transl Med. 7: 308re8.
More group Clotilde Wiel publications on PubMed