Matriptase activation and shedding with HAI-1 is induced by steroid sex hormones in human prostate cancer cells, but not in breast cancer cells

Kiyomiya, Ken-ichi; Lee, Ming-Shyue; Tseng, I-Chu; Zuo, Hong Xiang; Barndt, Robert J.; Johnson, Michael D.; Dickson, Robert B.; Lin, Chen‐Yong

doi:10.1152/ajpcell.00351.2005

Cited by 51 publications

(47 citation statements)

References 58 publications

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“…Among them, matriptase has been focused on because it plays crucial roles in carcinogenesis and cancer cell invasion including prostate cancer (9)(10)(11)(12). In prostate cancer cells, androgens can induce matriptase activation and shedding (13). However, the molecular mechanism through which androgens induce matriptase activation and whether the androgen-induced proteolytic cascade plays a role in prostate cancer progression and metastasis are still unknown.…”

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confidence: 99%

Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis

et al. 2015

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Dysregulation of androgen signaling and pericellular proteolysis is necessary for prostate cancer progression, but the links between them are still obscure. In this study, we show how the membrane-anchored serine protease TMPRSS2 stimulates a proteolytic cascade that mediates androgen-induced prostate cancer cell invasion, tumor growth, and metastasis. We found that matriptase serves as a substrate for TMPRSS2 in mediating this proinvasive action of androgens in prostate cancer. Further, we determined that higher levels of TMPRSS2 expression correlate with higher levels of matriptase activation in prostate cancer tissues. Lastly, we found that the ability of TMPRSS2 to promote prostate cancer tumor growth and metastasis was associated with increased matriptase activation and enhanced degradation of extracellular matrix nidogen-1 and laminin b1 in tumor xenografts. In summary, our results establish that TMPRSS2 promotes the growth, invasion, and metastasis of prostate cancer cells via matriptase activation and extracellular matrix disruption, with implications to target these two proteases as a strategy to treat prostate cancer.

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Section: Introductionmentioning

confidence: 99%

Androgen-Induced TMPRSS2 Activates Matriptase and Promotes Extracellular Matrix Degradation, Prostate Cancer Cell Invasion, Tumor Growth, and Metastasis

et al. 2015

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“…Matriptase autoactivation is induced by an array of structurally unrelated molecules in a relatively cell type-specific manner. For example, we have shown that matriptase activation is induced by the lysophospholipid sphingosine 1-phosphate in mammary epithelial cells (5) and by androgens in LNCaP prostate cancer cells (18). Although matriptase expression is observed in almost all epithelial tissues in vivo, matriptase activation is limited (42).…”

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confidence: 99%

“…This activation step converts the singlechain matriptase zymogen to a two-chain active form (4,31). Matriptase zymogen activation is controlled by exogenous stimuli (5,18,20) and dependent upon assembly of the activation complex (20). Matriptase autoactivation is induced by an array of structurally unrelated molecules in a relatively cell type-specific manner.…”

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confidence: 99%

Increased matriptase zymogen activation in inflammatory skin disorders

Chen¹,

Wu²,

Tsao³

et al. 2011

American Journal of Physiology-Cell Physiology

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Matriptase, a type 2 transmembrane serine protease, and its inhibitor hepatocyte growth factor activator inhibitor (HAI)-1 are required for normal epidermal barrier function, and matriptase activity is tightly regulated during this process. We therefore hypothesized that this protease system might be deregulated in skin disease. To test this, we examined the level and activation state of matriptase in examples of 23 human skin disorders. We first examined matriptase and HAI-1 protein distribution in normal epidermis. Matriptase was detected at high levels at cell-cell junctions in the basal layer and spinous layers but was present at minimal levels in the granular layer. HAI-1 was distributed in a similar pattern, except that high-level expression was retained in the granular layer. This pattern of expression was retained in most skin disorders. We next examined the distribution of activated matriptase. Although activated matriptase is not detected in normal epidermis, a dramatic increase is seen in keratinocytes at the site of inflammation in 16 different skin diseases. To gain further evidence that activation is associated with inflammatory stimuli, we challenged HaCaT cells with acidic pH or H2O2 and observed matriptase activation. These findings suggest that inflammation-associated reactive oxygen species and tissue acidity may enhance matriptase activation in some skin diseases.

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“…tion linked to spatial redistribution include suramin and androgens in prostate cancer cells (18). The ability of the matriptase zymogen to become activated and presented on the cell surface may depend on the direct physical interaction with its cognate Kunitz-type serine protease inhibitor HAI-1 ( Figure 1B).…”

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confidence: 99%