CXCR6-CXCL16 axis promotes prostate cancer by mediating cytoskeleton rearrangement via Ezrin activation and αvβ3 integrin clustering

Oncotarget
Rajesh SinghShailesh Singh

Abstract

Cytoskeletal rearrangement is required for migration and invasion, which are the key steps of cancer metastasis. Ezrin and integrin co-ordinate these processes by regulating cellular adhesion and cytoskeletal polymerization-depolymerization. It is also well established that chemokine-chemokine receptor axis plays a crucial role in regulating cancer cell migration and invasion. In this study, we show involvement of CXC chemokine receptor 6 (CXCR6) and its only natural ligand CXCL16 in pathobiology of prostate cancer (PCa). CXCR6 is highly expressed in PCa tissues and cell lines (LNCaP and PC3), relative to normal tissue and cells. CXCR6 expression in PCa tissues correlated with higher Gleason score. Similarly, aggressive PCa cells (PC3) show high CXCR6 compared to less aggressive LNCaP. Besides, PC3 cells show higher MMPs expression compared to LNCaP cells following CXCL16 stimulation. Intriguingly, CXCR6-CXCL16 interaction in PCa cells promotes Ezrin activation, αvβ3 integrin clustering and capping at the leading edge in FAK/PI3K/PKC dependent manner, thereby modifying cellular adhesion as well as motility. Together these results demonstrate that CXCL16 stimulation changes cytoskeletal dynamics resulting in enhanced migration, ...Continue Reading

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Citations

Jan 13, 2018·Journal of Cellular Biochemistry·Shishir UpadhyayMonisha Dhiman
Jul 13, 2017·International Journal of Molecular Sciences·Vivian AdamskiKirsten Hattermann
Nov 21, 2017·Oncotarget·Kiera Rycaj, Dean G Tang
Nov 3, 2017·Calcified Tissue International·Sun H ParkYusuke Shiozawa
Mar 7, 2017·Mediators of Inflammation·D DreymuellerA Ludwig
Jun 27, 2020·International Journal of Molecular Sciences·Timothy O Adekoya, Ricardo M Richardson
Sep 3, 2016·Journal of Hematology & Oncology·Stefan WilopBehzad Kharabi Masouleh
Aug 6, 2019·Canadian Respiratory Journal : Journal of the Canadian Thoracic Society·Sheng ZuoShaojun Yin
Jan 31, 2020·Frontiers in Cell and Developmental Biology·Juan ZhouSan-Gang Wu
Jan 9, 2021·Frontiers in Immunology·Shahid HussainRamesh K Ganju
May 4, 2020·Developmental and Comparative Immunology·Dan HeYan Li
Apr 4, 2021·International Journal of Molecular Sciences·Jan KorbeckiIrena Baranowska-Bosiacka
Apr 22, 2021·Expert Reviews in Molecular Medicine·Arezoo Gowhari ShabgahJamshid Gholizadeh Navashenaq
Apr 30, 2021·Cellular Oncology (Dordrecht)·Bikashita Kalita, Mohane Selvaraj Coumar

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Methods Mentioned

BETA
ELISA
electrophoresis
flow cytometry

Software Mentioned

Image Data Exploration and Analysis Software ( IDEAS )
ImageJ
Image Data Exploration Analysis ( IDEA )
Image stream system
IDEAS®
Inspire®
ImageStream100
IDEA ( Image Data Exploration and Analysis )

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