A Broad Survey of Cathepsin K Immunoreactivity in Human Neoplasms

Zheng, Gang; Martignoni, Guido; Antonescu, Cristina R.; Montgomery, Elizabeth A.; Eberhart, Charles G.; Netto, George J.; Taube, Janis M.; Westra, William H.; Epstein, Jonathan I.; Lotan, Tamara L.; Maitra, Anirban; Gabrielson, Edward; Torbenson, Michael; Iacobuzio‐Donahue, Christine A.; DeMarzo, Angelo M.; Shih, Ie Ming; Illei, Peter P.B.; Wu, T. C.; Argani, Pedram

doi:10.1309/ajcpdtrto2z4uexd

Cited by 44 publications

(30 citation statements)

References 26 publications

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“…1B). In a clinical study, cathepsin K staining revealed high expression in 65% of melanomas (21). Data from normal skin is available in the databases, but because MC constitute only a small fraction (approximately 3%) of the cells in the epidermis, we did not consider these data.…”

Section: Expression Of Cathepsins In Melanoma Cellsmentioning

confidence: 99%

Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases

Eding¹,

Domert²,

Wäster³

et al. 2014

Acta Derm Venerol

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Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melano-cyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression.

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Section: Expression Of Cathepsins In Melanoma Cellsmentioning

confidence: 99%

Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases

Eding¹,

Domert²,

Wäster³

et al. 2014

Acta Derm Venerol

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“…4 TFEB is a master transcriptional regulator of lysosomal biogenesis 5 and translocation carcinomas overexpress lysosomal proteases. 6 TFEB is also implicated in other functions like autophagy, 7 endocytosis, 8 exocytosis, 9 lipid metabolism, 10 the antiviral response, 11 and lysosomal calcium signaling. 12 Mice deficient for Tfeb/Tcfeb die at midgestation due to deficient placental vascularization 13 and may exhibit defects in endoderm development.…”

Section: Introductionmentioning

confidence: 99%

Multistep regulation of TFEB by MTORC1

et al. 2017

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The master regulator of lysosome biogenesis, TFEB, is regulated by MTORC1 through phosphorylation at S211, and a S211A mutation increases nuclear localization. However, TFEB S211A localizes diffusely in both cytoplasm and nucleus and, as we show, retains regulation by MTORC1. Here, we report that endogenous TFEB is phosphorylated at S122 in an MTORC1-dependent manner, that S122 is phosphorylated in vitro by recombinant MTOR, and that S122 is important for TFEB regulation by MTORC1. Specifically, nuclear localization following MTORC1 inhibition is blocked by a S122D mutation (despite S211 dephosphorylation). Furthermore, such a mutation inhibits lysosomal biogenesis induced by Torin1. These data reveal a novel mechanism of TFEB regulation by MTORC1 essential for lysosomal biogenesis.

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“…Unlike melanoma, clear cell sarcoma has a reciprocal translocation t (12:22) resulting in the fusion of EWS RNA-binding protein 1 (EWSR1) with activating transcription factor 1 (ATF1) in more than 90% of cases. In a study performed by Zheng et al, 23 cathepsin K showed positivity in 3 of 12 cases (25%) of clear cell sarcoma (one showed focal positivity). They suggested that a diffuse staining pattern favors ASPS.…”

Section: Differential Diagnosismentioning

confidence: 91%

Alveolar Soft Part Sarcoma

Jaber¹,

Kirby

2015

Archives of Pathology &Amp; Laboratory Medicine

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Alveolar soft part sarcoma is a rare neoplasm usually arising in the soft tissues of the lower limbs in adults and in the head and neck region in children. It presents primarily as a slowly growing mass or as metastatic disease. It is characterized by a specific chromosomal alteration, der(17)t(X:17)(p11:q25), resulting in fusion of the transcription factor E3 (TFE3) with alveolar soft part sarcoma critical region 1 (ASPSCR1) at 17q25. This translocation is diagnostically useful because the tumor nuclei are positive for TFE3 by immunohistochemistry. Real-time polymerase chain reaction to detect the ASPSCR1-TFE3 fusion transcript on paraffin-embedded tissue blocks has been shown to be more sensitive and specific than detection of TFE3 by immunohistochemical stain. Cathepsin K is a relatively recent immunohistochemical stain that can aid in the diagnosis. The recent discovery of the role of the ASPSCR1-TFE3 fusion protein in the MET proto-oncogene signaling pathway promoting angiogenesis and cell proliferation offers a promising targeted molecular therapy.

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A Broad Survey of Cathepsin K Immunoreactivity in Human Neoplasms

Cited by 44 publications

References 26 publications

Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases

Melanoma Growth and Progression After Ultraviolet A Irradiation: Impact of Lysosomal Exocytosis and Cathepsin Proteases

Multistep regulation of TFEB by MTORC1

Alveolar Soft Part Sarcoma

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