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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

Influence of SOX2 on oncogenic-related processes and transcription. (A) SOX2 is an important regulator of cellular processes related to cancer. Some of these processes include but aren’t limited to WNT/β-CATENIN signaling, EMT and JAK/STAT3 signaling. In most cases, SOX2 functions downstream in the nucleus. SOX2’s activity leads to further downstream effects and finally alters cellular phenotypes such as cellular survival, invasion and metastasis. (B) SOX2 is typically regulating processes downstream on a transcriptional level. There are several examples of SOX2 influencing cancer phenotypes by repressing or activating particular target genes including EMT promotion via binding to the promoter regions of SNAIL, SLUG and TWIST. Therefore, SOX2 functions in cancer as a key transcription factor.
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Figure 2: Influence of SOX2 on oncogenic-related processes and transcription. (A) SOX2 is an important regulator of cellular processes related to cancer. Some of these processes include but aren’t limited to WNT/β-CATENIN signaling, EMT and JAK/STAT3 signaling. In most cases, SOX2 functions downstream in the nucleus. SOX2’s activity leads to further downstream effects and finally alters cellular phenotypes such as cellular survival, invasion and metastasis. (B) SOX2 is typically regulating processes downstream on a transcriptional level. There are several examples of SOX2 influencing cancer phenotypes by repressing or activating particular target genes including EMT promotion via binding to the promoter regions of SNAIL, SLUG and TWIST. Therefore, SOX2 functions in cancer as a key transcription factor.

Mentions: As described by Hanahan and Weinberg, cancer is a disease characterized by determined hallmarks some of which are: sustained proliferative signaling, activation of invasion and metastasis, and evasion of cell death [73]. Studies have strongly associated SOX2 to these respective cancer hallmarks and thus far SOX2 has been shown to promote cellular proliferation (breast, prostate, pancreatic and cervical cancers) [21,28,57,58], evade apoptotic signals (prostate, gastric cancer and NSCLC) [37,58,63] and promote invasion, migration and metastasis (melanoma, colorectal, glioma, gastric, ovarian cancer and hepatocellular carcinoma) [15,29,47,49,55]. We summarized SOX2 amplification and resulting alterations in cellular functions in all cancer types in Table 1 and showed examples of SOX2’s role in oncogenic signaling in Figure 2. Below we highlight a few functional examples of SOX2 in cancer before we review the latest SOX2 research in different aspects of cancer physiology including: cellular proliferation, apoptosis and invasion/migration/metastasis. For a complementary and closer examination into SOX2 and oncogenic signaling, protein-protein interactions and miRNAs see review by Liu et al.[74].


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

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

Influence of SOX2 on oncogenic-related processes and transcription. (A) SOX2 is an important regulator of cellular processes related to cancer. Some of these processes include but aren’t limited to WNT/β-CATENIN signaling, EMT and JAK/STAT3 signaling. In most cases, SOX2 functions downstream in the nucleus. SOX2’s activity leads to further downstream effects and finally alters cellular phenotypes such as cellular survival, invasion and metastasis. (B) SOX2 is typically regulating processes downstream on a transcriptional level. There are several examples of SOX2 influencing cancer phenotypes by repressing or activating particular target genes including EMT promotion via binding to the promoter regions of SNAIL, SLUG and TWIST. Therefore, SOX2 functions in cancer as a key transcription factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Influence of SOX2 on oncogenic-related processes and transcription. (A) SOX2 is an important regulator of cellular processes related to cancer. Some of these processes include but aren’t limited to WNT/β-CATENIN signaling, EMT and JAK/STAT3 signaling. In most cases, SOX2 functions downstream in the nucleus. SOX2’s activity leads to further downstream effects and finally alters cellular phenotypes such as cellular survival, invasion and metastasis. (B) SOX2 is typically regulating processes downstream on a transcriptional level. There are several examples of SOX2 influencing cancer phenotypes by repressing or activating particular target genes including EMT promotion via binding to the promoter regions of SNAIL, SLUG and TWIST. Therefore, SOX2 functions in cancer as a key transcription factor.
Mentions: As described by Hanahan and Weinberg, cancer is a disease characterized by determined hallmarks some of which are: sustained proliferative signaling, activation of invasion and metastasis, and evasion of cell death [73]. Studies have strongly associated SOX2 to these respective cancer hallmarks and thus far SOX2 has been shown to promote cellular proliferation (breast, prostate, pancreatic and cervical cancers) [21,28,57,58], evade apoptotic signals (prostate, gastric cancer and NSCLC) [37,58,63] and promote invasion, migration and metastasis (melanoma, colorectal, glioma, gastric, ovarian cancer and hepatocellular carcinoma) [15,29,47,49,55]. We summarized SOX2 amplification and resulting alterations in cellular functions in all cancer types in Table 1 and showed examples of SOX2’s role in oncogenic signaling in Figure 2. Below we highlight a few functional examples of SOX2 in cancer before we review the latest SOX2 research in different aspects of cancer physiology including: cellular proliferation, apoptosis and invasion/migration/metastasis. For a complementary and closer examination into SOX2 and oncogenic signaling, protein-protein interactions and miRNAs see review by Liu et al.[74].

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