BCL9 Provides Multi-cellular Communication Properties in Colorectal Cancer by Interacting with Paraspeckle Proteins

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jan 9

PMID 31911584

Citations 21

Authors

Meng Jiang

Yue Kang

Tomasz Sewastianik

Jiao Wang

Helen Tanton

Keith Alder

Peter Dennis

Yu Xin

Zhongqiu Wang

Ruiyang Liu

Mengyun Zhang

Ying Huang

Massimo Loda

Amitabh Srivastava

Runsheng Chen

Ming Liu

Ruben D Carrasco

Affiliations

Soon will be listed here.

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and neural associated genes. In response to spontaneous calcium transients or cellular stress, BCL9 is recruited adjacent to the interchromosomal regions, where it stabilizes the mRNA of calcium signaling and neural associated genes by interacting with paraspeckle proteins. BCL9 subsequently promotes tumor progression and remodeling of the tumor microenvironment (TME) by sustaining the calcium transients and neurotransmitter-dependent communication among CRC cells. These data provide additional insights into the role of BCL9 in tumor pathogenesis and point towards additional avenues for therapeutic intervention.

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