The hyaluronan-mediated motility receptor RHAMM promotes growth, invasiveness and dissemination of colorectal cancer.

Mele, Valentina; Sokol, Lena; Kölzer, Viktor; Pfaff, Dennis; Muraro, Manuele Giuseppe; Keller, Irene; Zahnd, Stefan Patrick; Centeno Ramos, Irene; Terracciano, Luigi Maria; Dawson, Heather; Zlobec, Inti; Iezzi, Giandomenica; Lugli, Alessandro (2017). The hyaluronan-mediated motility receptor RHAMM promotes growth, invasiveness and dissemination of colorectal cancer. OncoTarget, 8(41), pp. 70617-70629. Impact Journals LLC 10.18632/oncotarget.19904

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In colorectal cancer (CRC), RHAMM is an independent adverse prognostic factor. The aim of the study was therefore to investigate on the role of RHAMM as a potential direct driver of cell proliferation and migration in CRC cell lines and to identify pathways dependent on RHAMM in human CRC. Proliferation, cell cycle alterations and invasive capacity were tested in two RHAMM- and control- knockdown CRC cell lines by flow cytometry and in vitro assays. Tumorigenicity and metastasis formation was assessed in immunodeficient mice. RNA-Seq and immunohistochemistry was performed on six RHAMM+/- primary CRC tumors. In vitro, silencing of RHAMM inhibited CRC cell migration and invasion by 50% (p<0.01). In vivo, RHAMM knockdown resulted in slower growth, lower tumor size (p<0.001) and inhibition of metastasis (p<0.001). Patients with RHAMM-high CRC had a worse prognosis (p=0.040) and upregulated pathways for cell cycle progression and adhesion turnover. RHAMM overexpression is correlated with increased migration and invasion of CRC cells, leads to larger, fast growing tumors, and its downregulation essentially abolishes metastasis in mouse models. RHAMM is therefore a promising therapeutic target in all CRC stages as its inhibition affects growth and dissemination of the primary CRC as well as the metastases.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Translational Research Unit
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Genomics
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology

UniBE Contributor:

Sokol, Lena; Kölzer, Viktor; Keller, Irene; Zahnd, Stefan Patrick; Centeno Ramos, Irene; Dawson, Heather; Zlobec, Inti and Lugli, Alessandro

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1949-2553

Publisher:

Impact Journals LLC

Language:

English

Submitter:

Inti Zlobec

Date Deposited:

31 Jan 2018 16:19

Last Modified:

31 Jan 2018 16:26

Publisher DOI:

10.18632/oncotarget.19904

PubMed ID:

29050306

Uncontrolled Keywords:

RHAMM colorectal cancer invasion metastasis proliferation

BORIS DOI:

10.7892/boris.110620

URI:

https://boris.unibe.ch/id/eprint/110620

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