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As part of the National Collegiate Honors Council’s (2022) collection of essays about the value of honors to its graduates (1967–2019), the author reflects on the personal and professional impacts of the honors experience. The year was 1989. I had moved from a rural community in Michigan to South Carolina to attend Columbia College, a private, liberal-arts women’s college. The culture shock and adjustment were equal parts exhilarating and unnerving. I was welcomed by the warm, Southern charm of campus and was nurtured, personally and academically, by the close-knit community of the honors program. I had a rich college experience in general, but being an honors student changed the entire trajectory of my career and shaped me personally, instilling confidence, motivation, and purpose. The indelible mark stemmed from the program’s motto: Non Magis Sed Melior, “Not More, but Better.” The program was intentionally grounded not in the quantity of coursework but in the quality, delivering a deep academic experience that challenged students to reach their highest potential as scholars and leaders.

Fibroblast Growth Factor-1 (FGF-1) is a potent mitogen and angiogenic factor found in both normal and malignant tissues. FGF-1 mediates its diverse biological effects by binding to and activation of its high-affinity tyrosine kinase receptors, initiating a myriad of signaling cascades. Evidence indicates that the act of receptor engagement by the FGF ligand is insufficient for transduction of a full proliferative signal. it is speculated that FGF-FGFR internalization and its subsequent processing may play an active role in completing the mitogenic signal. The reported studies indicate that the FGF-1 mitogenic signal requires ligand endocytosis via the "classical" clathrin-mediated pathway and exposure to an acidic compartment. Furthermore, both a pepstatin- and leupeptin-sensitive event(s) appear critical for a full mitogenic response. Given the implicated role for a number of different proteases in contributing to the breast cancer pathology, this protease-sensitive activity in FGF-1 signaling is under investigation. FGF-1 has been reported to progress breast carcinomas from a hormone-dependent state to a hormone-independent state and from nonmetastatic to metastatic. Therefore, better understanding the mechanism of FGF-1 signaling could provide additional avenues for adjuvant therapies. An antimitogenic approach to treatment of breast cancer would have a broader efficacy, not limited by the hormone-responsive state of the tumor.

Cathepsin D was initially thought to be an individual prognostic indictor for the disease state of human breast cancers. Over the years, the data substantiating such a role for cathepsin D has been quite conflicting However, there is strong evidence that cathepsin D plays a role in the degradation of the extracellular matrix (ECM) and basement membrane surrounding tumors. In doing so, cathepsin D is an active participant in releasing ECM-bound growth factors, one of which is FGF-1. FGF-1 is a potent mitogen and angiogenic factor found in both normal and malignant tissues. FGF-1 mediates its effects by binding to its cognate receptor. Evidence indicates that the act of ligand biding to the receptor is insufficient for transduction of the mitogenic signal. It is speculated that FGF-FGFR internalization and its subsequent processing may play an active role in completing the mitogenic signal. The reported studies indicate FGF-1 is internalized into clathrin-coated< vesicles by the classical," receptor- mediated endocytic pathway. Upon disruption of internalization and processing pharmacological inhibitors, FGF-1 mitogenic activity is hindered. Furthermore, pretreatment of FGF-1 stimulated cells with an inhibitor of the major lysosomal proteases, cathepsin D, results in a reduction in the mitogenic response. Therefore, a cathepsin-ID-like activity and possibly other cellular proteases may be participants in the FGF-1 signal transduction pathway A small, linear fragment of FGF-1 has been identified that mimics, in some instances, the mitogenic bioactivity of the intact growth factor, supporting the notion that a processed form of FGF may have an intracellular role in signaling. Breast carcinomas are characterized by the overexpression and secretion of various proteases, one of which is cathepsin D. Consequently, cathepsin D may play a coordinated role with FGF-1 in tumor progression and invasion.