XB130—A Novel Adaptor Protein: Gene, Function, and Roles in Tumorigenesis

Abstract

Several adaptor proteins have previously been shown to play an important role in the promotion of tumourigenesis. XB130 (AFAP1L2) is an adaptor protein involved in many cellular functions, such as cell survival, cell proliferation, migration, and gene and miRNA expression. XB130's functional domains and motifs enable its interaction with a multitude of proteins involved in several different signaling pathways. As a tyrosine kinase substrate, tyrosine phosphorylated XB130 associates with the p85α regulatory subunit of phosphoinositol-3-kinase (PI3K) and subsequently affects Akt activity and its downstream signalling. Tumourigenesis studies show that downregulation of XB130 expression by RNAi inhibits tumor growth in mouse xenograft models. Furthermore, XB130 affects tumor oncogenicity by regulating the expression of specific tumour suppressing miRNAs. The expression level and pattern of XB130 has been studied in various human tumors, such as thyroid, esophageal, and gastric cancers, as well as, soft tissue tumors. Studies show the significant effects of XB130 in tumourigenesis and suggest its potential as a diagnostic biomarker and therapeutic target for cancer treatments.

XB130, regulated by miR‐203, miR‐219, and miR‐4782‐3p, mediates the proliferation and metastasis of non‐small‐cell lung cancer cells

“…Bioinformatics analysis has shown that the top diseases and cellular functions related to XB130 are cancers and cell growth, respectively 11 . Therefore, XB130 has been predicted to be an oncogene and a potential diagnostic marker and therapeutic target for cancers 3,4 . But after that, in 2019, XB130 has been reported to be a tumor suppressor in skin tumorigenesis induced by carcinogen through inhibiting inflammation, 12 which was in contrast with previous conclusions and indicated that XB130 may play different roles in different tumors.…”

“…XB130, also known as actin filament associated protein 1‐like 2, is a novel multifunctional adapter protein 3‐5 . First, XB130 crosslinks actin filaments (F‐actin), promoting cell endocytosis, migration, and invasion 6,7 .…”

“…6,7 Second, XB130 phosphorylated by tyrosine kinase (protooncogene tyrosine-protein kinase [Src], rearranged during transfection proto-oncogene/papillary thyroid carcinoma, lymphocyte cell kinase, epidermal growth factor receptor, Abelson tyrosine-protein kinase 1, or erb-b2 receptor tyrosine kinase 2) can interact with proteins containing Src Homology 2 (SH2) and SH3 domains, such as Src, GAP, PLCγ, and P85α subunits of phosphatidylinositol-3-kinase (PI3K), which will subsequently activate related signaling pathways downstream and mediate cell proliferation, metastasis, inflammatory, and innate immune response. 3,[8][9][10] Altered expressions of 246 genes and 38 microRNAs (miRNAs) were observed after XB130 knockdown in human thyroid cancer cell WRO. 11 Bioinformatics analysis has shown that the top diseases and cellular functions related to XB130 are cancers and cell growth, respectively.…”

Knockdown of XB130 restrains cancer stem cell‐like phenotype through inhibition of Wnt/β‐Catenin signaling in breast cancer

“…XB130, an adaptor protein, is discovered in the molecular cloning of actin filament‐associated protein (AFAP) . Adapter proteins are a unique group of protein binding partners.…”

Stimulus-dependent dissociation between XB130 and Tks5 scaffold proteins promotes airway epithelial cell migration

“…Several scaffold proteins have been implicated in the regulation of cell migration, such as the growth factor receptor-bound protein (Grb) family, tyrosine kinase substrate (Tks) family and non-catalytic region of tyrosine kinase adaptor protein (Nck) family [4-6]. XB130 is a scaffold protein that belongs to the actin filament associated protein family and acts as a signal transduction molecule to mediate cell growth, survival and cytoskeleton remodeling [7]. …”