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. 2018 Aug 17;5(4):e1458016.
doi: 10.1080/23723556.2018.1458016. eCollection 2018.

EnABLing Cathepsin-Driven Melanoma Metastasis

Rakshamani Tripathi  1 , Rina Plattner  1
Affiliations

EnABLing Cathepsin-Driven Melanoma Metastasis

Rakshamani Tripathi et al. Mol Cell Oncol. .

Abstract

Metastatic melanoma remains incurable for many due to its aggressive nature. Secreted cathepsins promote metastasis by cleaving matrix and activating pro-invasive proteases. We reported that ABL kinases induce cathepsin secretion and subsequent metastasis by activating ETS1, SP1, and RELA pathways, indicating that ABL inhibitors may serve as novel anti-cathepsin agents.

Keywords: ABL1; ABL2; Abl; Arg; ETS1; NF-κB; RELA; SP1; cathepsin; cysteine cathepsins.

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Figures

Figure 1.
Figure 1.
ABL kinase regulation of cathepsin secretion in melanoma. ABL1/ABL2 are activated by receptor tyrosine kinases (RTKs), SRC Family Kinases (SFK) and BRAF-ERK, and subsequently induce SP1, ETS1, and RELA expression/nuclear translocation, and binding to cathepsin promoters. These events induce cathepsin transcription, secretion, invasion, and metastasis. PM: Plasma Membrane; ER: Endoplasmic Reticulum; and ECM: Extracellular Matrix.
See this image and copyright information in PMC

References

    1. Olson OC, Joyce JA. Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response. Nat Rev Cancer. 2015;15(12): 712–29. - PubMed
    1. Sudhan DR, Siemann DW. Cathepsin L targeting in cancer treatment. Pharmacol Ther. 2015;155:105–16. - PMC - PubMed
    1. Ganguly SS, Plattner R. Activation of Abl family kinases in solid tumors. Genes Cancer. 2012;3(5-6):414–25. - PMC - PubMed
    1. Fiore LS, Ganguly S, Sledziona J, Cibull ML, Wang C, Richards DL, Neltner JM, Beach C, McCorkle JR, Kaetzel DM, et al. . c-Abl and Arg induce cathepsin-mediated lysosomal degradation of the NM23-H1 metastasis suppressor in invasive cancer. Oncogene. 2014;33(36):4508–20. - PMC - PubMed
    1. Ganguly SS, Fiore LS, Sims JT, Friend JW, Srinivasan D, Thacker MA, et al. . c-Abl and Arg are activated in human primary melanomas, promote melanoma cell invasion via distinct pathways, and drive metastatic progression. Oncogene. 2012;31(14):1804–16. - PMC - PubMed

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