FHL2: A scaffold protein of carcinogenesis, tumour-stroma interactions and treatment response

Laurine Verset¹, Lynn Feys², Anne-Laure Trépant¹, Olivier De Wever² and Pieter Demetter<sup>1

1</sup>Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles, Bruxelles and ²Laboratory of Experimental Cancer Research, Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium

Offprint requests to: Pieter Demetter, MD, PhD, Department of Pathology, Erasme University Hospital, Route de Lennik 808, 1070 Brussels, Belgium. e-mail: pieter.demetter@erasme.ulb.ac.be

Summary. Four-and-a-half LIM-domain protein 2 (FHL2) is a multifunctional scaffolding protein regulating signalling cascades and gene transcription. It shuttles between focal adhesions and the nucleus where it signals through direct interaction with a number of proteins including β-catenin. The multiplicity of molecular pathways affected by FHL2 suggests an important role in several physiological and pathological events. The function of FHL2 in cancer is particularly intriguing, since it may act as an oncoprotein or as a tumour suppressor in a tissue-dependent fashion. In this review we present the current knowledge on the role of FHL2 in carcinogenesis, with emphasis on the digestive tract. We discuss the overexpression of FHL2 in colorectal, gastric and pancreatic cancer, the downregulation in hepatocellular carcinoma and the role of FHL2 in epithelial-mesenchymal transition. We briefly look at the potential role of FHL2 in the tumoural microenvironment and discuss how FHL2 expression and function might influence cancer treatment. Before implementation of FHL2 as a biomarker by pathologists, antibody validation should, however, be carried out. Histol Histopathol 31, 469-478 (2016)

Key words: FHL2, Carcinogenesis, Digestive tract

DOI: 10.14670/HH-11-709