Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance
Articolo
Data di Pubblicazione:
2024
Citazione:
Dissecting the Puzzling Roles of FAM46C: A Multifaceted Pan-Cancer Tumour Suppressor with Increasing Clinical Relevance / G. Lai, F. DE GROSSI, I. Catusi, E. Pesce, N. Manfrini. - In: CANCERS. - ISSN 2072-6694. - 16:9(2024), pp. 1706.1-1706.23. [10.3390/cancers16091706]
Abstract:
FAM46C is a well-established tumour suppressor with a role that is not completely defined
or universally accepted. Although FAM46C expression is down-modulated in several tumours,
significant mutations in the FAM46C gene are only found in multiple myeloma (MM). Consequently,
its tumour suppressor activity has primarily been studied in the MM context. However, emerging
evidence suggests that FAM46C is involved also in other cancer types, namely colorectal, prostate
and gastric cancer and squamous cell and hepatocellular carcinoma, where FAM46C expression
was found to be significantly reduced in tumoural versus non-tumoural tissues and where FAM46C
was shown to possess anti-proliferative properties. Accordingly, FAM46C was recently proposed to
function as a pan-cancer prognostic marker, bringing FAM46C under the spotlight and attracting
growing interest from the scientific community in the pathways modulated by FAM46C and in its
mechanistic activity. Here, we will provide the first comprehensive review regarding FAM46C by
covering (1) the intracellular pathways regulated by FAM46C, namely the MAPK/ERK, PI3K/AKT,
β-catenin and TGF-β/SMAD pathways; (2) the models regarding its mode of action, specifically
the poly(A) polymerase, intracellular trafficking modulator and inhibitor of centriole duplication
models, focusing on connections and interdependencies; (3) the regulation of FAM46C expression
in different environments by interferons, IL-4, TLR engagement or transcriptional modulators; and,
lastly, (4) how FAM46C expression levels associate with increased/decreased tumour cell sensitivity
to anticancer agents, such as bortezomib, dexamethasone, lenalidomide, pomalidomide, doxorubicin,
melphalan, SK1-I, docetaxel and norcantharidin.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
autophagy; multiple myeloma; PLK4; poly(A) polymerase; TENT5C; tumour suppressor
Elenco autori:
G. Lai, F. DE GROSSI, I. Catusi, E. Pesce, N. Manfrini
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