Sarah T. Diepstraten
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Previous Organizations / Institutes
The organizations / institutes from the scholar's other articles in the past ten years
Research Subjects
Research Interests
Sarah T. Diepstraten has a total of 26 co-authors. Here are the top co-authors by number of shared publications:
- Gemma L. Kelly
The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia
3 shared publications - Andreas Strasser
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia
2 shared publications Aisling M. Ross
Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; School of Medicine, Bernal Institute, Limerick Digital Cancer Research Centre & Health Research Institute, University of Limerick, Limerick, Ireland
1 shared publicationAndreas Strasser
Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia
1 shared publicationAndrew H. Wei
Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC 3050, Australia
1 shared publicationAndrew W. Roberts
Blood Cells and Blood Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia; Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC 3050, Australia
1 shared publication
Latest Publications
- 7 October 2024
- Published by Elsevier in Developmental Cell
- Vol. 59 (19) , 2532-2548
Don’t fear the reaper: The role of regulated cell death in tumorigenesis and BH3-mimetics for cancer therapy
- 7 October 2024
- Published by Elsevier in Developmental Cell
- Vol. 59 (19) , 2532-2548
Don’t fear the reaper: The role of regulated cell death in tumorigenesis and BH3-mimetics for cancer therapy
- Open Access
- 25 April 2024
- Published by Elsevier in Cancer Cell
- Vol. 42 (5) , 850-868.e9
Putting the STING back into BH3-mimetic drugs for TP53-mutant blood cancers
- 25 April 2024
- Published by Elsevier in Cancer Cell
- Vol. 42 (5) , 850-868.e9
Open AccessPutting the STING back into BH3-mimetic drugs for TP53-mutant blood cancers
- Open Access
Loss of mutant TP53 does not impair the sustained proliferation, survival or metastasis of diverse cancer cells
The tumour suppressor TP53 is the most frequently mutated gene in human cancer and these aberrations confer poor chemotherapeutic responses 1-3 . Point mutations typically cluster in the DNA binding domain, with certain ‘hot-spot’ residues disproportionally represented 1-4 These mutations abrogate binding of the TP53 transcription factor to DNA and thereby prevent upregulation of genes critical for tumour suppression (loss-of-function) 1-3 . Mutant TP53 is reported to additionally contribute to tumour development, sustained growth and metastasis not only through dominant-negative effects on wild-type TP53 5 but also through neomorphic gain-of-function (GOF) activities 6 . Understanding the contributions of these postulated attributes of mutant TP53 to the development and expansion of tumours will facilitate the design of rational therapeutic strategies. Here we used CRISPR/CAS9 to delete mutant TP53 in a panel of diverse human cancer cell lines. The loss of mutant TP53 expression had no impact on the survival, proliferative capacity or metabolic state of the tumour cells, nor did it sensitise them to cellular stresses and chemotherapeutic agents. These data suggest that putative GOF effects of mutant TP53 are not universally required for the sustained survival and proliferation of fully malignant cells. Therefore, therapeutic approaches that abrogate expression or function of mutant TP53 would not be expected to have substantial impact.
Open AccessLoss of mutant TP53 does not impair the sustained proliferation, survival or metastasis of diverse cancer cells
The tumour suppressor TP53 is the most frequently mutated gene in human cancer and these aberrations confer poor chemotherapeutic responses 1-3 . Point mutations typically cluster in the DNA binding domain, with certain ‘hot-spot’ residues disproportionally represented 1-4 These mutations abrogate binding of the TP53 transcription factor to DNA and thereby prevent upregulation of genes critical for tumour suppression (loss-of-function) 1-3 . Mutant TP53 is reported to additionally contribute to tumour development, sustained growth and metastasis not only through dominant-negative effects on wild-type TP53 5 but also through neomorphic gain-of-function (GOF) activities 6 . Understanding the contributions of these postulated attributes of mutant TP53 to the development and expansion of tumours will facilitate the design of rational therapeutic strategies. Here we used CRISPR/CAS9 to delete mutant TP53 in a panel of diverse human cancer cell lines. The loss of mutant TP53 expression had no impact on the survival, proliferative capacity or metabolic state of the tumour cells, nor did it sensitise them to cellular stresses and chemotherapeutic agents. These data suggest that putative GOF effects of mutant TP53 are not universally required for the sustained survival and proliferation of fully malignant cells. Therefore, therapeutic approaches that abrogate expression or function of mutant TP53 would not be expected to have substantial impact.