Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers

Jin-Ah Kim, Ying Tan, Xian Wang, Xixi Cao, Jamunarani Veeraraghavan, Yulong Liang, Dean P. Edwards, Shixia Huang, Xuewen Pan, Kaiyi Li, Rachel Schiff and Xiao-Song Wang ()
Additional contact information
Jin-Ah Kim: Lester & Sue Smith Breast Center, Baylor College of Medicine
Ying Tan: Lester & Sue Smith Breast Center, Baylor College of Medicine
Xian Wang: Lester & Sue Smith Breast Center, Baylor College of Medicine
Xixi Cao: Lester & Sue Smith Breast Center, Baylor College of Medicine
Jamunarani Veeraraghavan: Lester & Sue Smith Breast Center, Baylor College of Medicine
Yulong Liang: Baylor College of Medicine
Dean P. Edwards: Dan L. Duncan Cancer Center, Baylor College of Medicine
Shixia Huang: Dan L. Duncan Cancer Center, Baylor College of Medicine
Xuewen Pan: Baylor College of Medicine
Kaiyi Li: Baylor College of Medicine
Rachel Schiff: Lester & Sue Smith Breast Center, Baylor College of Medicine
Xiao-Song Wang: Lester & Sue Smith Breast Center, Baylor College of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: Abstract More aggressive and therapy-resistant oestrogen receptor (ER)-positive breast cancers remain a great clinical challenge. Here our integrative genomic analysis identifies tousled-like kinase 2 (TLK2) as a candidate kinase target frequently amplified in ∼10.5% of ER-positive breast tumours. The resulting overexpression of TLK2 is more significant in aggressive and advanced tumours, and correlates with worse clinical outcome regardless of endocrine therapy. Ectopic expression of TLK2 leads to enhanced aggressiveness in breast cancer cells, which may involve the EGFR/SRC/FAK signalling. Conversely, TLK2 inhibition selectively inhibits the growth of TLK2-high breast cancer cells, downregulates ERα, BCL2 and SKP2, impairs G1/S cell cycle progression, induces apoptosis and significantly improves progression-free survival in vivo. We identify two potential TLK2 inhibitors that could serve as backbones for future drug development. Together, amplification of the cell cycle kinase TLK2 presents an attractive genomic target for aggressive ER-positive breast cancers.

Date: 2016
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms12991 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12991

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms12991

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().