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Review
. 2022 Oct 28;2(1):R143-R152.
doi: 10.1530/EO-22-0055. eCollection 2022 Jan.

Role of filamin A in the pathogenesis of neuroendocrine tumors and adrenal cancer

Donatella Treppiedi  1 , Rosa Catalano  1 , Federica Mangili  1 , Giovanna Mantovani  1   2 , Erika Peverelli  1   2
Affiliations
Review

Role of filamin A in the pathogenesis of neuroendocrine tumors and adrenal cancer

Donatella Treppiedi et al. Endocr Oncol. .

Abstract

Cell cytoskeleton proteins are involved in tumor pathogenesis, progression and pharmacological resistance. Filamin A (FLNA) is a large actin-binding protein with both structural and scaffold functions implicated in a variety of cellular processes, including migration, cell adhesion, differentiation, proliferation and transcription. The role of FLNA in cancers has been studied in multiple types of tumors. FLNA plays a dual role in tumors, depending on its subcellular localization, post-translational modification (as phosphorylation at Ser2125) and interaction with binding partners. This review summarizes the experimental evidence showing the critical involvement of FLNA in the complex biology of endocrine tumors. Particularly, the role of FLNA in regulating expression and signaling of the main pharmacological targets in pituitary neuroendocrine tumors, pancreatic neuroendocrine tumors, pulmonary neuroendocrine tumors and adrenocortical carcinomas, with implications on responsiveness to currently used drugs in the treatment of these tumors, will be discussed.

Keywords: ACC; FLNA; P-NETs; Pan-NETs; PitNETs.

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Conflict of interest statement

The authors have no conflict of interest to declare.

Figures

Figure 1
Figure 1
Schematic representation of an FLNA monomer. The structure of FLNA is schematically represented with the N-terminus domain containing the actin-binding site, followed by 24 immunoglobulin(Ig)-like repeats organized into rod domains: rod-1 (repeats 1–15), rod-2 (repeats 16–23) and repeat 24 that mediates homodimerization. Rod-1 and rod-2 are separated by a flexible hinge region (H1) and another hinge (H2) separates repeats 23 and 24. Both H1 and H2 are calpain cleavage sites. In repeat 20, the nuclear localization signal (NLS) and the phosphorylation site, serine 2152, are indicated. The region of 41 amino acids (repeats 19–20) deleted in the splice var-1 of FLNA is shown.
Figure 2
Figure 2
FLNA in endocrine tumors. The figure schematically represents the proposed models of FLNA involvement in regulating expression and functions of different receptors (DRD2, SSTR2, SSTR5, IGF1R, IR) specifically present in neuroendocrine tumors (PRL-, GH- and ACTH-secreting pituitary tumors, pancreatic and pulmonary neuroendocrine tumors, adrenocortical carcinomas).
See this image and copyright information in PMC

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