CD44 and RHAMM Are Microenvironmental Sensors with Dual Metastasis Promoter and Suppressor Functions

Cornelia Tolg; Kathleen Allen Hill; Eva Ann Turley

doi:10.1002/adbi.202300693

CD44 and RHAMM Are Microenvironmental Sensors with Dual Metastasis Promoter and Suppressor Functions

Adv Biol (Weinh). 2024 Apr 18:e2300693. doi: 10.1002/adbi.202300693. Online ahead of print.

Authors

Cornelia Tolg¹, Kathleen Allen Hill², Eva Ann Turley^{1

3}

Affiliations

¹ Cancer Research Laboratory Program, Lawson Health Research Institute, Victoria Hospital, London, ON, N6A 5W9, Canada.
² Department of Biology, Western University, London, ON, N6A 3K7, Canada.
³ Departments of Oncology, Biochemistry, and Surgery, Western University, London, ON, N6A 5W9, Canada.

PMID: 38638002
DOI: 10.1002/adbi.202300693

Abstract

The progression of primary tumors to metastases remains a significant roadblock to the treatment of most cancers. Emerging evidence has identified genes that specifically affect metastasis and are potential therapeutic targets for managing tumor progression. However, these genes can have dual tumor promoter and suppressor functions that are contextual in manifestation, and that complicate their development as targeted therapies. CD44 and RHAMM/HMMR are examples of multifunctional proteins that can either promote or suppress metastases, as demonstrated in experimental models. These two proteins can be viewed as microenvironmental sensors and this minireview addresses the known mechanistic underpinnings that may determine their metastasis suppressor versus promoter functions. Leveraging this mechanistic knowledge for CD44, RHAMM, and other multifunctional proteins is predicted to improve the precision of therapeutic targeting to achieve more effective management of metastasis.

Keywords: HMMR; RHAMM; duality; hyaluronan; metastasis; mouse models; tissue context; tumor promoter; tumor suppressor.

Publication types

Review

Grants and funding

#945897/CAPMC/ CIHR/Canada