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SOX2 and cancer: current research and its implications in the clinic.

Weina K, Utikal J - Clin Transl Med (2014)

Bottom Line: Consequently, SOX2 functions as an activator or suppressor of gene transcription.SOX2 research has only recently switched focus from embryogenesis and development to SOX2's function in disease.Recent reviews in this field have highlighted SOX2 in mammalian physiology, development and pathology.

View Article: PubMed Central - HTML - PubMed

Affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany ; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany.

ABSTRACT
SOX2 is a gene that encodes for a transcription factor belonging to the SOX gene family and contains a high-mobility group (HMG) domain, which permits highly specific DNA binding. Consequently, SOX2 functions as an activator or suppressor of gene transcription. SOX2 has been described as an essential embryonic stem cell gene and moreover, a necessary factor for induced cellular reprogramming. SOX2 research has only recently switched focus from embryogenesis and development to SOX2's function in disease. Particularly, the role of SOX2 in cancer pathogenesis has become of interest in the field. To date, studies have shown SOX2 to be amplified in various cancer types and affect cancer cell physiology via involvement in complicated cell signaling and protein-protein interactions. Recent reviews in this field have highlighted SOX2 in mammalian physiology, development and pathology. In this review, we comprehensively compile what is known to date about SOX2's involvement in cancer biology, focusing on the most recent findings in the fields of cellular signaling and cancer stem cells. Lastly, we underscore the role of SOX2 in the clinic and highlight new findings, which may provide novel clinical applications for SOX2 as a prognostic marker, indicator of metastasis, biomarker or potential therapeutic target in some cancer types.

No MeSH data available.


Related in: MedlinePlus

SOX2 homology, structure and protein function. (A) SOX2 belongs to the SOXB1 of SOX proteins. There is large homology between the SOXB1 group and they all contain three major domains: N-terminal, HMG and C-terminal domain. (B) SOX2 protein domains play several functional roles. The HMG domain of SOX2 remains fairly conserved between homo sapiens, Mus musculus and Danio rerio (Swiss-Prot: P48431, P48432, Q6P0E1). The HMG domain also serves as potential binding sites for protein partners. Moreover, nuclear import signals (NIS) and nuclear export signals (NES) bind to the HMG domain regulating SOX2 itself. Lastly the transactivation domain functions as the region responsible for promoter binding, which in turn leads to activation or repression of target genes.
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Figure 1: SOX2 homology, structure and protein function. (A) SOX2 belongs to the SOXB1 of SOX proteins. There is large homology between the SOXB1 group and they all contain three major domains: N-terminal, HMG and C-terminal domain. (B) SOX2 protein domains play several functional roles. The HMG domain of SOX2 remains fairly conserved between homo sapiens, Mus musculus and Danio rerio (Swiss-Prot: P48431, P48432, Q6P0E1). The HMG domain also serves as potential binding sites for protein partners. Moreover, nuclear import signals (NIS) and nuclear export signals (NES) bind to the HMG domain regulating SOX2 itself. Lastly the transactivation domain functions as the region responsible for promoter binding, which in turn leads to activation or repression of target genes.

Mentions: In 1994, the SOX2 gene, one of the SOX family members, was discovered and characterized in humans [7]. The SOX2 gene is located on chromosome 3q26.3–q27, belongs to the SOXB1 group and encodes for a protein consisting of 317 amino acids (Figure 1A) [7,8]. SOX2 is comprised of three main domains: N-terminal, HMG and transactivation domain (Figure 1B). SOX2 research thus far has heavily emphasized its crucial role in stem cell maintenance, lineage fate determinant and a necessary factor to reprogram somatic cells back towards pluripotency [5,9,10]. In disease, SOX2 alterations have been associated with developmental maladies, such as anophthalmia-esophageal-genital (AEG) syndrome, which occurs when there is a heterozygous mutation of SOX2 that leads to abnormal development of ectodermal and endodermal tissues [11]. Aside from developmental diseases, accruing research has strongly associated SOX2 with cancer.


SOX2 and cancer: current research and its implications in the clinic.

Weina K, Utikal J - Clin Transl Med (2014)

SOX2 homology, structure and protein function. (A) SOX2 belongs to the SOXB1 of SOX proteins. There is large homology between the SOXB1 group and they all contain three major domains: N-terminal, HMG and C-terminal domain. (B) SOX2 protein domains play several functional roles. The HMG domain of SOX2 remains fairly conserved between homo sapiens, Mus musculus and Danio rerio (Swiss-Prot: P48431, P48432, Q6P0E1). The HMG domain also serves as potential binding sites for protein partners. Moreover, nuclear import signals (NIS) and nuclear export signals (NES) bind to the HMG domain regulating SOX2 itself. Lastly the transactivation domain functions as the region responsible for promoter binding, which in turn leads to activation or repression of target genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126816&req=5

Figure 1: SOX2 homology, structure and protein function. (A) SOX2 belongs to the SOXB1 of SOX proteins. There is large homology between the SOXB1 group and they all contain three major domains: N-terminal, HMG and C-terminal domain. (B) SOX2 protein domains play several functional roles. The HMG domain of SOX2 remains fairly conserved between homo sapiens, Mus musculus and Danio rerio (Swiss-Prot: P48431, P48432, Q6P0E1). The HMG domain also serves as potential binding sites for protein partners. Moreover, nuclear import signals (NIS) and nuclear export signals (NES) bind to the HMG domain regulating SOX2 itself. Lastly the transactivation domain functions as the region responsible for promoter binding, which in turn leads to activation or repression of target genes.
Mentions: In 1994, the SOX2 gene, one of the SOX family members, was discovered and characterized in humans [7]. The SOX2 gene is located on chromosome 3q26.3–q27, belongs to the SOXB1 group and encodes for a protein consisting of 317 amino acids (Figure 1A) [7,8]. SOX2 is comprised of three main domains: N-terminal, HMG and transactivation domain (Figure 1B). SOX2 research thus far has heavily emphasized its crucial role in stem cell maintenance, lineage fate determinant and a necessary factor to reprogram somatic cells back towards pluripotency [5,9,10]. In disease, SOX2 alterations have been associated with developmental maladies, such as anophthalmia-esophageal-genital (AEG) syndrome, which occurs when there is a heterozygous mutation of SOX2 that leads to abnormal development of ectodermal and endodermal tissues [11]. Aside from developmental diseases, accruing research has strongly associated SOX2 with cancer.

Bottom Line: Consequently, SOX2 functions as an activator or suppressor of gene transcription.SOX2 research has only recently switched focus from embryogenesis and development to SOX2's function in disease.Recent reviews in this field have highlighted SOX2 in mammalian physiology, development and pathology.

View Article: PubMed Central - HTML - PubMed

Affiliation: Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany ; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karls-Universität Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany.

ABSTRACT
SOX2 is a gene that encodes for a transcription factor belonging to the SOX gene family and contains a high-mobility group (HMG) domain, which permits highly specific DNA binding. Consequently, SOX2 functions as an activator or suppressor of gene transcription. SOX2 has been described as an essential embryonic stem cell gene and moreover, a necessary factor for induced cellular reprogramming. SOX2 research has only recently switched focus from embryogenesis and development to SOX2's function in disease. Particularly, the role of SOX2 in cancer pathogenesis has become of interest in the field. To date, studies have shown SOX2 to be amplified in various cancer types and affect cancer cell physiology via involvement in complicated cell signaling and protein-protein interactions. Recent reviews in this field have highlighted SOX2 in mammalian physiology, development and pathology. In this review, we comprehensively compile what is known to date about SOX2's involvement in cancer biology, focusing on the most recent findings in the fields of cellular signaling and cancer stem cells. Lastly, we underscore the role of SOX2 in the clinic and highlight new findings, which may provide novel clinical applications for SOX2 as a prognostic marker, indicator of metastasis, biomarker or potential therapeutic target in some cancer types.

No MeSH data available.


Related in: MedlinePlus