SOX2 enhances the migration and invasion of ovarian cancer cells via Src kinase
Authors: Zhenbo Zhang
Jiazhou Chen
Dong Yan
Xiaowei Xi
Youji Feng
Qifeng Wang
Xiaojie Wang
Xiaoning Ji
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Ovarian cancer; SOX2; metastasis; proliferation; migration
Affiliations: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China., Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, China.

Abstract:  Ovarian cancer is the leading cause of death among gynecologic cancers and is the fifth leading cause of all cancer-related deaths among women. The development of novel molecular targets is therefore important to many patients. Recently, the SRY-related transcription factor SOX2 has been widely reported to be involved in multiple pathophysiological diseases, including maintenance of stem cell characteristics and carcinogenesis. Up to now, SOX2 has been mainly shown to promote the development of cancer, although its inhibitory roles in cancer have also been reported. However, the role of SOX2 in ovarian cancer is largely unknown. In the present study, we detected the expression of SOX2 in 64 human serous ovarian carcinoma (SOC) tissues and paired corresponding metastatic specimens using immunohistochemistry. The results showed that the expression of SOX2 in primary tumors is much lower than that in the corresponding metastatic lesions. We further found that SOX2 overexpression promotes proliferation, migration and invasion, while inhibiting adhesion abilities of SOC cells. Finally, we found that SOX2 targets Src kinase, a non-receptor tyrosine kinase that regulates cell migration, invasion and adhesion in SOC cells. Together, these results suggested that Src kinase is a key molecule in SOX2-mediated migration and invasion of SOC cells. 

Retracted: No

PubPeer comments:
 Several concerns were shared with the journal in October 2015, but no action as of today. * Figure 6B: Two MMP-2 panels, representing HO8910 and Skov3 cells, respectively, appear to look similar if one of them is rotated 180 degrees. Marked with green boxes. ![file] * Figures 4A and 7A: Two sets of panels appear too look very similar. The ones marked with cyan boxes might represent the same experiments, but the ones marked with red boxes appear to show different experiments. ![file] , 
 #1 Dear sir, Thank you for your comment on our article. As an retired scientific worker,I have left my hospital for 5 years. I will contact to you after I have discussed it with the first auther of the article. Best regards. Youji Feng , 
 This paper states to use  Ovarian cancer cell lines Hey, HO8910, and HO8910-pm were obtained from the American Type Culture Collection First HO8910 and HO8910-pm were never distributed by ATCC. They were established in China and only distributed by Chinese cell collections. So this statement is not correct. What is more problematic is that these two cell lines are not ovarian cell lines but are HeLa contaminated. This fact was not known when this paper was published so the authors are not to be blamed but it unfortunatly means that all the conclusions as relevant to ovarian cancer are not correct. See the relevant [Cellosaurus entry] , 
 Figure 6B, a redo from October 2015, with a couple more years or experience. Some more duplications might be visible, some with mirroring or rotation. Do the authors have any additional comments or insights what happened here? ![file] , 
 #4 Figs 6B, 7B ![file] , 
 The image duplications that I list in this comment are **not the fault of the present authors**. A papermill or mills appropriated the present migration invasion images from Figures 4A B C and 7A, and details from them appear in a large number of fraudulent papers. I want to stress that I am listing those papers here only to have a convenient central location and not as a criticism of the present authors, who have my sympathy.  Crk-like adapter protein regulates CCL19 CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas ([Cheng et al 2015] ). *[left]* Fig 4b. *[right]* The present Fig 4A B. ![file] ------------------------------------  Long non-coding RNA MALAT1 is up-regulated in ovarian cancer tissue and promotes SK-OV-3 cell proliferation and invasion ([Zou et al 2016] ). Fig 3A C. ![file] The present Fig 4B C: ![] -----------------------------------  MicroRNA-182 suppresses clear cell renal cell carcinoma migration and invasion by targeting IGF1R ([Wang et al 2016] ). Figs 3A,C and 5C,E: ![] The present Fig 4A B: ![] -------------------------------------  miR-186 affects the proliferation, invasion and migration of human gastric cancer by inhibition of Twist1 ([Cao et al 2016] ). Fig 3a,b. ![file] The present Figs 4A, 7A. ![file] ---------------------------  Block of proliferation 1 promotes cell migration and invasion in human colorectal cancer cells via the JNK pathway ([Chen Zhao 2020] ). Figs 2D, 3E, 5A: ![file] Colored rectangles indicate the sources of panels in the present Figs 4A,B. ![file] The remaining panels match the present Fig 4C but I was running out of colors. -----------------------------------  FDPS promotes glioma growth and macrophage recruitment by regulating CCL20 via Wnt u03b2u2010catenin signalling pathway ([Chen et al 2020] ). Fig 3A B: ![] The present Figs 4A, 7A: ![] ------------------------ The present Figures 3B, D, F were also appropriated. Below, at right. At left is Fig 3B from  miR-139 is up-regulated in osteoarthritis and inhibits chondrocyte proliferation and migration possibly via suppressing EIF4G2 and IGF1R ([Hu et al 2016] ). ![] , 
 #6 Continuing this list of papers that appropriated the present migration invasion images from Figures 4A B C and 7A. I repeat the caveat that this was not the fault of the present authors.  MicroRNA-940 Targets INPP4A or GSK3u03b2 and Activates the Wnt u03b2-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells ([Wang et al 2018] ). Fig 3: ![] Fig 6 G I from  miR-203 Suppresses Bladder Cancer Cell Growth and Targets Twist1 ([Shen et al 2018] ). ![] Fig 3A C from  MicroRNA-1277 Inhibits Proliferation and Migration of Hepatocellular Carcinoma HepG2 Cells by Targeting and Suppressing BMP4 Expression and Reflects the Significant Indicative Role in Hepatocellular Carcinoma Pathology and Diagnosis After Magnetic Resonance Imaging Assessment ([Cao et al 2019] ) ![] All extensively remixed from the present Fig 4A B. ![] -------------------------  CUL4B promotes aggressive phenotypes of HNSCC via the activation of the Wnt u03b2u2010catenin signaling pathway ([Wang Yue 2019] ). Figures 2E-H, and 4B C -- rotated through 90 deg for ease of comparison. ![] The present 4A B: ![] -------------------------------  miRu2010126 reduces trastuzumab resistance by targeting PIK3R2 and regulating AKT mTOR pathway in breast cancer cells ([Fu Tong 2020] ). Fig 2 E-H: ![] The present Fig 4A B C. ![] ----------------------  SETDB1 promotes glioblastoma growth via CSF-1-dependent macrophage recruitment by activating the AKT mTOR signaling pathway ([Han et al 2020] ). Fig 3A D (U251 panels only). ![] The present Fig 4A B C: ![] -------------------------------  miRu20101254 inhibits progression of glioma in vivo and in vitro by targeting CSFu20101 ([Li et al 2020] ). Fig 2H: ![] The present Fig 4A, 7A: ![] Fig 5G: ![] The present 4B C: ![] -------------------------------------  Up-regulation of DNA2 results in cell proliferation and migration in endometriosis ([Wang et al 2021] ). Fig 4b, and the present 4A B C. ![] -------------------- *[left]* Fig Fig 3A C from  Long non-coding RNA SNHG16 promotes cell growth and metastasis in ovarian cancer ([Yang et al 2018] ). Some of the panels were extracted from [right] Figs 4B, 7A. ![] ------------------------------- Figs 4A, 7A again... ![] This time with Fig 2E from  BET inhibitor I-BET151 sensitizes GBM cells to temozolomide via PUMA induction ([Yao et al 2020] ). ![file] ,