Home
Resources
Publications
The LINK-A lncRNA Activates Normoxic HIF1α Signalling in Triple-Negative Breast Cancer

The LINK-A lncRNA Activates Normoxic HIF1α Signalling in Triple-Negative Breast Cancer

Aifu Lin, Chunlai Li, Zhen Xing, Qingsong Hu, Ke Liang, Leng Han, Cheng Wang, David H Hawke, Shouyu Wang, Yanyan Zhang, Yongkun Wei, Guolin Ma, Peter K Park, Jianwei Zhou, Yan Zhou, Zhibin Hu, Yubin Zhou, etc.

Nat Cell Biol. 2016 Feb;18(2):213-24.

PMID: 26751287

Abstract:

Although long non-coding RNAs (lncRNAs) predominately reside in the nucleus and exert their functions in many biological processes, their potential involvement in cytoplasmic signal transduction remains unexplored. Here, we identify a cytoplasmic lncRNA, LINK-A (long intergenic non-coding RNA for kinase activation), which mediates HB-EGF-triggered, EGFR:GPNMB heterodimer-dependent HIF1α phosphorylation at Tyr 565 and Ser 797 by BRK and LRRK2, respectively. These events cause HIF1α stabilization, HIF1α-p300 interaction, and activation of HIF1α transcriptional programs under normoxic conditions. Mechanistically, LINK-A facilitates the recruitment of BRK to the EGFR:GPNMB complex and BRK kinase activation. The BRK-dependent HIF1α Tyr 565 phosphorylation interferes with Pro 564 hydroxylation, leading to normoxic HIF1α stabilization. Both LINK-A expression and LINK-A-dependent signalling pathway activation correlate with triple-negative breast cancer (TNBC), promoting breast cancer glycolysis reprogramming and tumorigenesis. Our findings illustrate the magnitude and diversity of cytoplasmic lncRNAs in signal transduction and highlight the important roles of lncRNAs in cancer.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR424671	Phalloidin-Atto 565			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: