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Your search keyword '"Dhwani N. Rupani"' showing total 2 results
Start Over Author "Dhwani N. Rupani" Journal nature cancer
2 results on '"Dhwani N. Rupani"'

1. APOBEC3A drives deaminase domain-independent chromosomal instability to promote pancreatic cancer metastasis

Author

Meifang Yu, Jason B. Fleming, Rena Levin-Klein, Steven Gallinger, Susan R. Ross, Cullen M. Taniguchi, Chris Gates, Dhwani N. Rupani, Sara L. Manning, Runsheng Wang, Michael P. Kim, Kimal I. Rajapakshe, Fredrik I. Thege, Reuben S. Harris, Weisheng Wu, S Wörmann, Matthew H G Katz, Faiyaz Notta, Asha S. Multani, Amy Zhang, Ya’an Kang, Anirban Maitra, Andrew D. Rhim, Ravikanth Maddipati, Melena D. Bellin, Robert W. Cowan, and Katharina Schlacher

Subjects
Cancer Research, Cancer, Cytidine deaminase, DNA Repair Pathway, Biology, medicine.disease, Metastasis, Oncology, Downregulation and upregulation, Chromosome instability, Pancreatic cancer, medicine, Cancer research, APOBEC3A
Abstract

Despite efforts in understanding its underlying mechanisms, the etiology of chromosomal instability (CIN) remains unclear for many tumor types. Here, we identify CIN initiation as a previously undescribed function for APOBEC3A (A3A), a cytidine deaminase upregulated across cancer types. Using genetic mouse models of pancreatic ductal adenocarcinoma (PDA) and genomics analyses in human tumor cells we show that A3A-induced CIN leads to aggressive tumors characterized by enhanced early dissemination and metastasis in a STING-dependent manner and independently of the canonical deaminase functions of A3A. We show that A3A upregulation recapitulates numerous copy number alterations commonly observed in patients with PDA, including co-deletions in DNA repair pathway genes, which in turn render these tumors susceptible to poly (ADP-ribose) polymerase inhibition. Overall, our results demonstrate that A3A plays an unexpected role in PDA as a specific driver of CIN, with significant effects on disease progression and treatment. Woermann and colleagues describe a deaminase-independent function for APOBEC3A in initiating chromosomal instability and STING-dependent metastasis in human and mouse pancreatic cancer.

Published
2021
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2. APOBEC3A drives deaminase domain-independent chromosomal instability to promote pancreatic cancer metastasis

Author

Sonja M, Wörmann, Amy, Zhang, Fredrik I, Thege, Robert W, Cowan, Dhwani N, Rupani, Runsheng, Wang, Sara L, Manning, Chris, Gates, Weisheng, Wu, Rena, Levin-Klein, Kimal I, Rajapakshe, Meifang, Yu, Asha S, Multani, Ya'an, Kang, Cullen M, Taniguchi, Katharina, Schlacher, Melena D, Bellin, Matthew H G, Katz, Michael P, Kim, Jason B, Fleming, Steven, Gallinger, Ravikanth, Maddipati, Reuben S, Harris, Faiyaz, Notta, Susan R, Ross, Anirban, Maitra, and Andrew D, Rhim

Subjects
Pancreatic Neoplasms, Mice, Chromosomal Instability, Cytidine Deaminase, Animals, Humans, Proteins
Abstract

Despite efforts in understanding its underlying mechanisms, the etiology of chromosomal instability (CIN) remains unclear for many tumor types. Here, we identify CIN initiation as a previously undescribed function for APOBEC3A (A3A), a cytidine deaminase upregulated across cancer types. Using genetic mouse models of pancreatic ductal adenocarcinoma (PDA) and genomics analyses in human tumor cells we show that A3A-induced CIN leads to aggressive tumors characterized by enhanced early dissemination and metastasis in a STING-dependent manner and independently of the canonical deaminase functions of A3A. We show that A3A upregulation recapitulates numerous copy number alterations commonly observed in patients with PDA, including co-deletions in DNA repair pathway genes, which in turn render these tumors susceptible to poly (ADP-ribose) polymerase inhibition. Overall, our results demonstrate that A3A plays an unexpected role in PDA as a specific driver of CIN, with significant effects on disease progression and treatment.

Published
2021

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