RETRACTED: Recruitment of Tiam1 to Semaphorin 4D Activates Rac and Enhances Proliferation, Invasion, and Metastasis in Oral Squamous Cell Carcinoma
Authors: Ying-Hua Yang
Emily K Mallory
Hua Zhou
Amr Bugshan
John R Basile
Nada O Binmadi
Maricel G Kann
Journal: Neoplasia (2017)
Discipline: CLINICAL MEDICINE
Keywords: Semaphorins; Plexins; Tumor growth; Reverse signaling; PB1
Affiliations: Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650 W. Baltimore Street, 7-North, Baltimore, MD 21201, USA., Dept of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA., Biomedical Informatics Training Program, Stanford University, 1265 Welch Road, Stanford, CA 94305, USA., Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650 W. Baltimore Street, 7-North, Baltimore, MD 21201, USA; Department of Oral Basic & Clinical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia., Department of Oncology and Diagnostic Sciences, University of Maryland Dental School, 650 W. Baltimore Street, 7-North, Baltimore, MD 21201, USA; Greenebaum Cancer Center, 22 S. Greene Street, Baltimore, MD 21201, USA. Electronic address: .

Abstract:  The semaphorins and the plexins are a family of large, cysteine-rich proteins originally identified as regulators of axon growth and lymphocyte activation that are now known to provide motility and positional information for a number of cell and tissue types. For example, our group and others have shown that some malignancies over express Semaphorin 4D (S4D), which acts through its receptor Plexin-B1 (PB1) on endothelial cells to attract blood vessels from the surrounding stroma for the purpose of supporting tumor growth. While plexins are the known functional receptors for the semaphorins, there is evidence that transmembrane semaphorins may transmit a signal themselves through their short cytoplasmic tail, a phenomenon known as 'reverse signaling.' We used computational methods based upon correlated evolution of sequences of interacting proteins, mutational analysis and in vitro and in vivo measurements of tumor aggressiveness to show that when bound to PB1, transmembrane S4D associates with the Rac GTPase exchange factor T lymphoma invasion and metastasis (Tiam) 1, which activates Rac and promotes proliferation, invasion and metastasis in oral squamous cell carcinoma (OSCC) cells. These results suggest that not only can S4D production by tumor cells affect the microenvironment, but engagement of this semaphorin at the cell surface activates a reverse signaling mechanism that influences tumor aggressiveness in OSCC. 

Retracted: Yes

PubPeer comments:
 2021 retraction. https: www.sciencedirect.com science article pii S1476558621000580?via%3Dihub This article is being retracted following correspondence from the Office of Accountability and Compliance at the University of Maryland, Baltimore. An internal investigation into this manuscript by the University of Maryland, Baltimore, found evidence that there are errors with the presentation of the data shown in Figures 4A, 4B, and 5A and that these inaccuracies warrant retraction to correct the scientific record. Figure 4A: The original data show that the cell line was HN13 instead of HN12 that was described in the paper; the averages were not calculated correctly; the time points were incorrectly reported. Figure 4B: The two images in column 2 came from the same micrograph; the four images in columns 3 and 4, which were supposed to be two separate conditions and two different cell lines, came from the same micrograph; the two images in column 5 came from the same micrograph. Figure 5A: There was discrepancy with regard to the stated antibody. The legend states that the image was immunohistochemistry for SEMA4D instead of for PB1 as indicated in the figure labels. , 
 https: retractionwatch.com 2020 04 22 a-year-after-a-university-asked-two-elsevier-journals-to-retract-papers-they-havent ,