Functional characterization of SOX2 as an anticancer target
TL;DR: This review briefly introduced SOX2 as a transcription factor, its domain structure, normal physiological functions, and its involvement in human cancers and its role in embryonic development and stem cell-renewal.
read more
Abstract: SOX2 is a well-characterized pluripotent factor that is essential for stem cell self-renewal, reprogramming, and homeostasis. The cellular levels of SOX2 are precisely regulated by a complicated network at the levels of transcription, post-transcription, and post-translation. In many types of human cancer, SOX2 is dysregulated due to gene amplification and protein overexpression. SOX2 overexpression is associated with poor survival of cancer patients. Mechanistically, SOX2 promotes proliferation, survival, invasion/metastasis, cancer stemness, and drug resistance. SOX2 is, therefore, an attractive anticancer target. However, little progress has been made in the efforts to discover SOX2 inhibitors, largely due to undruggable nature of SOX2 as a transcription factor. In this review, we first briefly introduced SOX2 as a transcription factor, its domain structure, normal physiological functions, and its involvement in human cancers. We next discussed its role in embryonic development and stem cell-renewal. We then mainly focused on three aspects of SOX2: (a) the regulatory mechanisms of SOX2, including how SOX2 level is regulated, and how SOX2 cross-talks with multiple signaling pathways to control growth and survival; (b) the role of SOX2 in tumorigenesis and drug resistance; and (c) current drug discovery efforts on targeting SOX2, and the future perspectives to discover specific SOX2 inhibitors for effective cancer therapy.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
Characterization of Temozolomide Resistance Using a Novel Acquired Resistance Model in Glioblastoma Cell Lines
Yuan Zhu,Zhen Chen,Su Na Kim,Chao Gan,Tatsiana Ryl,Michaela S. Lesjak,Jan Rodemerk,Rong Zhong,Karsten H. Wrede,Philipp Dammann,Ulrich Sure +10 more
TL;DR: An acute TMZ resistance model is established that recapitulates key features of TMZ resistance involving impaired mismatch repair, redistribution of cell cycle phases, increased DNA replication, reduced apoptosis and enhanced self-renewal and is believed to be a promising model to study the underlying mechanisms and define therapeutics for GBM in the future.
Additional file 1 of Inhibiting NR5A2 targets stemness in pancreatic cancer by disrupting SOX2/MYC signaling and restoring chemosensitivity
Zheng Quan,Tang Jia-jia,Aicher, Alexandra,Chen MinChun,He Bin,Alcala Sonia,Behrens Diana,Scarpa Aldo,Hidalgo, Manuel,Sainz Bruno,Heeschen, Christopher +10 more
- 28 Nov 2023
Abstract: Additional file 1: Supplementary Table 1. cDNA primer sequences. Supplementary Table 2. Genomic DNA primer sequences. Supplementary Table 3. Genetic targeting of NR5A2.
The long noncoding RNA MIR4435-2HG enhances the migration, promotion, and glycolysis of nonsmall cell lung cancer cells by targeting the miR-371a-5p/SOX2/PI3K/Akt axis
Jing Wang,Yu‐Chieh Su,Sheng Wang,Kun Gao,Chuang Li,Mengmeng Li +5 more
TL;DR: MIR4435-2HG promotes nonsmall cell lung cancer cell migration, glycolysis, and proliferation by targeting the miR-371a-5p/SOX2/PI3K/Akt axis, highlighting its carcinogenic role in NSCLC and potential as a therapeutic target.
Surrogate Immunohistochemical Markers of Proliferation and Embryonic Stem Cells in Distinguishing Ameloblastoma from Ameloblastic Carcinoma
Liam Robinson,Chané Smit,Marlene B. van Heerden,Haroon Moolla,Amir Afrogheh,Johan Opperman,Melvin A. Ambele,Willie F. P. van Heerden +7 more
TL;DR: This study investigates the use of surrogate immunohistochemical markers to distinguish ameloblastoma from ameloblastic carcinoma, finding that Ki-67 proliferation index is helpful in differentiation, but SOX2, OCT4, and GPC-3 markers are unreliable.
Noncoding RNA circuitry in melanoma onset, plasticity, and therapeutic response.
Katerina Grafanaki,Ioannis Grammatikakis,Vishaka Gopalan,Gül Olgun,Huaitian Liu,George Kyriakopoulos,Ilias Skeparnias,S. Georgiou,Constantinos Stathopoulos,Sridhar Hannenhalli,G. Merino,Kerrie L. Marie,Chi-Ping Day +12 more
TL;DR: In this paper , a review of noncoding RNA-mediated mechanisms for melanoma was presented, including microRNAs, long non-coding RNAs, circular RNAs and other small RNAs.
References
Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.
TL;DR: Induction of pluripotent stem cells from mouse embryonic or adult fibroblasts by introducing four factors, Oct3/4, Sox2, c-Myc, and Klf4, under ES cell culture conditions is demonstrated and iPS cells, designated iPS, exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
27K
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Sendurai A. Mani,Wenjun Guo,Mai Jing Liao,Elinor Ng Eaton,Ayyakkannu Ayyanan,Alicia Y. Zhou,Mary W. Brooks,Ferenc Reinhard,Cheng Cheng Zhang,Michail Shipitsin,Lauren L. Campbell,Kornelia Polyak,Cathrin Brisken,Jing Yang,Robert A. Weinberg +14 more
TL;DR: It is reported that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers, and it is shown that those cells have an increased ability to form mammospheres, a property associated with mammARY epithelial stem cells.
9K
Molecular mechanisms of epithelial–mesenchymal transition
TL;DR: The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues, and the convergence of signalling pathways is essential for EMT.
7.6K
Smad-dependent and Smad-independent pathways in TGF-beta family signalling.
Rik Derynck,Ying E. Zhang +1 more
TL;DR: Transforming growth factor-β (TGF-β) proteins regulate cell function, and have key roles in development and carcinogenesis, and combinatorial interactions in the heteromeric receptor and Smad complexes, receptor-interacting and Smadracing proteins, and cooperation with sequence-specific transcription factors allow substantial versatility and diversification of TGF- β family responses.
5.2K
Core transcriptional regulatory circuitry in human embryonic stem cells.
Laurie A. Boyer,Tong Ihn Lee,Megan F. Cole,Sarah E. Johnstone,Stuart S. Levine,Jacob P. Zucker,Matthew G. Guenther,Roshan M. Kumar,Heather L. Murray,Richard G. Jenner,David K. Gifford,David K. Gifford,David K. Gifford,Douglas A. Melton,Douglas A. Melton,Rudolf Jaenisch,Richard A. Young,Richard A. Young +17 more
TL;DR: Insight is provided into the transcriptional regulation of stem cells and how OCT4, SOX2, and NANOG contribute to pluripotency and self-renewal and how they collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops.
4.7K