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Review
. 2024 Jan 29:14:1309687.
doi: 10.3389/fonc.2024.1309687. eCollection 2024.

Two decades of a protooncogene TBL1XR1: from a transcription modulator to cancer therapeutic target

Ruijuan Du  1   2 , Kai Li  1   2 , KeLei Guo  1   2 , Zhiguo Chen  1 , Xulin Zhao  3 , Li Han  1   2 , Hua Bian  1   2
Affiliations
Review

Two decades of a protooncogene TBL1XR1: from a transcription modulator to cancer therapeutic target

Ruijuan Du et al. Front Oncol. .

Abstract

Transducin beta-like 1X-related protein 1 (TBL1XR1) was discovered two decades ago and was implicated as part of the nuclear transcription corepressor complex. Over the past 20 years, the emerging oncogenic function of TBL1XR1 in cancer development has been discovered. Recent studies have highlighted that the genetic aberrations of TBL1XR1 in cancers, especially in hematologic tumors, are closely associated with tumorigenesis. In solid tumors, TBL1XR1 is proposed to be a promising prognostic biomarker due to the correlation between abnormal expression and clinicopathological parameters. Post-transcriptional and post-translational modification are responsible for the expression and function of TBL1XR1 in cancer. TBL1XR1 exerts its functional role in various processes that involves cell cycle and apoptosis, cell proliferation, resistance to chemotherapy and radiotherapy, cell migration and invasion, stemness and angiogenesis. Multitude of cancer-related signaling cascades like Wnt-β-catenin, PI3K/AKT, ERK, VEGF, NF-κB, STAT3 and gonadal hormone signaling pathways are tightly modulated by TBL1XR1. This review provided a comprehensive overview of TBL1XR1 in tumorigenesis, shedding new light on TBL1XR1 as a promising diagnostic biomarker and druggable target in cancer.

Keywords: TBL1XR1; oncogene; signaling pathways; therapeutic target; upstream regulators.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Structure of human TBL1XR1 protein. The protein structure was obtained from Protein Data Bank (https://www.rcsb.org/structure/4LG9). (A) The domain structure of human TBL1XR1. Monomeric assembly 1 of PDB entry 4lg9 was coloured by chemically distinct molecules and viewed from the front (B), the side (C) and the top (D).
Figure 2
Figure 2
Evolution tree of TBL1XR1. The highlight of discovery of TBL1XR1 and its significance in the field of cancer research.
Figure 3
Figure 3
Upstream regulators of TBL1XR1. (A) Post-transcriptional regulation of TBL1XR1 expression via miRNAs and lncRNAs. (B) SUMOylation of TBL1XR1 regulated activation of Wnt-β-catenin pathway.
Figure 4
Figure 4
Signaling axes modulated by TBL1XR1 in cancer.
Figure 5
Figure 5
TBL1XR1 in cancer. TBL1XR1 is involved in multiple processes of cancer occurrence and development. (A) Promoting cell proliferation. (B) Facilitating EMT, cell migration and invasion. (C) Promoting lymphangiogenesis. (D) Accelerating chemoresistance of cancer cell. (E) Facilitating stemness. (F) Inhibiting cell apoptosis and inducing cell cycle arrest.
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