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Cell surface receptors play crucial roles in cellular responses to extracellular ligands, helping to modulate the functions of a cell based on information coming from outside the cell. Syndecan refers to a family of cell adhesion receptors that regulate both extracellular and cytosolic events. Alteration of syndecan expression disrupts regulatory mechanisms in a cell type-specific fashion, often leading to serious diseases, notably cancer. Given the multifaceted functions and distinct tissue distributions of syndecan, it will be important to unravel the gene-level intricacies of syndecan expression and thereby further understand its involvement in various carcinogenic processes. Although accumulating evidence indicates that the protein expression patterns of syndecan family members are significantly altered in cancer cells, the underlying gene-level mechanisms remain largely unknown. This review endeavors to explore syndecan gene expression levels across different cancer types by scrutinizing extensive cancer genome datasets using tools such as cBioPortal. Our analysis unveils that somatic mutations in SDC genes are rare occurrences, whereas copy number alterations are frequently observed across diverse cancers, particularly in SDC2 and SDC4. Notably, amplifications of SDC2 and SDC4 correlate with heightened metastatic potential and dismal prognosis. This underscores the recurrent nature of SDC2 and SDC4 amplifications during carcinogenesis and sheds light on their role in promoting cancer activity through augmented protein expression. The identification of these amplifications not only enriches our understanding of carcinogenic mechanisms but also hints at the potential therapeutic avenue of targeting SDC2 and SDC4 to curb cancer cell proliferation and metastasis. [ABSTRACT FROM AUTHOR]

Introduction: The Plastic Surgery Integrated track remains one of the most competitive fields in the National Residency Match Program. Match trends during the COVID-19 pandemic featured a distinct rise in regional and home program matches among plastic surgery applicants. The purpose of this study is to evaluate whether these trends have continued into the most recent residency match cycle in 2024., Methods: Residency match data from 2019 to 2024 was gathered through the Accreditation Council for Graduate Medical Education, Electronic Residency Application Service, integrated plastic surgery program websites, and plastic surgery residency program social media accounts. Current trends were compared with match cycles before and during the pandemic., Results: After COVID, the number of students matching at their home institution decreased to rates consistent with prepandemic norms. In the 2024 cycle, 46.9% of applicants matched at integrated plastic surgery programs within the geographical region of their medical school, which is similar to pre-COVID rates. Further, the emergence of a female-predominant plastic surgery match cohort during the pandemic has continued. In 2024, 125 (58.7%) of 213 matched applicants into integrated plastic surgery programs were female, which represents a continuation of female-majority resident cohorts since 2021. Our data showed that a sizable component of matched applicants completed visiting student electives at their matched institution. Finally, a large number of matched applicants completed a research fellowship, and a historically stable number completed research fellowships at their matched institution., Conclusion: Our group reports stabilization in plastic surgery match trends in the wake of the COVID-19 pandemic, along with the continuation of growth in the number of female plastic surgery residents. Although home institution retention rates returned to the baseline proportionality exhibited prior to COVID-19, medical school geographical region may continue to play an important role in the integrated plastic surgery residency match., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Previous work showed that matrix metalloproteinase-7 (MMP-7) regulates colon cancer activities through an interaction with syndecan-2 (SDC-2) and SDC-2-derived peptide that disrupts this interaction and exhibits anticancer activity in colon cancer. Here, to identify potential anticancer agents, a library of 1,379 Food and Drug Administration (FDA)-approved drugs that interact with the MMP-7 prodomain were virtually screened by protein-ligand docking score analysis using the GalaxyDock3 program. Among five candidates selected based on their structures and total energy values for interacting with the MMP-7 prodomain, the known mechanistic target of rapamycin kinase (mTOR) inhibitor, everolimus, showed the highest binding affinity and the strongest ability to disrupt the interaction of the MMP-7 prodomain with the SDC-2 extracellular domain in vitro. Everolimus treatment of the HCT116 human colon cancer cell line did not affect the mRNA expression levels of MMP-7 and SDC-2 but reduced the adhesion of cells to MMP-7 prodomain-coated plates and the cell-surface localization of MMP-7. Thus, everolimus appears to inhibit the interaction between MMP-7 and SDC-2. Everolimus treatment of HCT116 cells also reduced their gelatin-degradation activity and anticancer activities, including colony formation. Interestingly, cells treated with sirolimus, another mTOR inhibitor, triggered less gelatin-degradation activity, suggesting that this inhibitory effect of everolimus was not due to inhibition of the mTOR pathway. Consistently, everolimus inhibited the colony-forming ability of mTOR-resistant HT29 cells. Together, these data suggest that, in addition to inhibiting mTOR signaling, everolimus exerts anticancer activity by interfering with the interaction of MMP-7 and SDC-2, and could be a useful therapeutic anticancer drug for colon cancer. NEW & NOTEWORTHY The utility of cancer therapeutics targeting the proteolytic activities of MMPs is limited because MMPs are widely distributed throughout the body and involved in many different aspects of cell functions. This work specifically targets the activation of MMP-7 through its interaction with syndecan-2. Notably, everolimus, a known mTOR inhibitor, blocked this interaction, demonstrating a novel role for everolimus in inhibiting mTOR signaling and impairing the interaction of MMP-7 with syndecan-2 in colon cancer.