PRSS2 remodels the tumor microenvironment via repression of Tsp1 to stimulate tumor growth and progression.
PRSS2 remodels the tumor microenvironment via repression of Tsp1 to stimulate tumor growth and progression.
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DOI：
10.1038/s41467-022-35649-9
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发表时间：
2022-12-27
影响因子：
16.6
通讯作者：
Watnick, Randolph S. S.
中科院分区：
文献类型：
--
作者：
Sui, Lufei;Wang, Suming;Ganguly, Debolina;El Rayes, Tyler P. P.;Askeland, Cecilie;Borretzen, Astrid;Sim, Danielle;Halvorsen, Ole Johan;Knutsvik, Goril;Arnes, Jarle;Aziz, Sura;Haukaas, Svein;Foulkes, William D. D.;Bielenberg, Diane R. R.;Ziemys, Arturas;Mittal, Vivek;Brekken, Rolf A. A.;Akslen, Lars A. A.;Watnick, Randolph S. S.
The progression of cancer from localized to metastatic disease is the primary cause of morbidity and mortality. The interplay between the tumor and its microenvironment is the key driver in this process of tumor progression. In order for tumors to progress and metastasize they must reprogram the cells that make up the microenvironment to promote tumor growth and suppress endogenous defense systems, such as the immune and inflammatory response. We have previously demonstrated that stimulation of Tsp-1 in the tumor microenvironment (TME) potently inhibits tumor growth and progression. Here, we identify a novel tumor-mediated mechanism that represses the expression of Tsp-1 in the TME via secretion of the serine protease PRSS2. We demonstrate that PRSS2 represses Tsp-1, not via its enzymatic activity, but by binding to low-density lipoprotein receptor-related protein 1 (LRP1). These findings describe a hitherto undescribed activity for PRSS2 through binding to LRP1 and represent a potential therapeutic strategy to treat cancer by blocking the PRSS2-mediated repression of Tsp-1. Based on the ability of PRSS2 to reprogram the tumor microenvironment, this discovery could lead to the development of therapeutic agents that are indication agnostic. Tsp-1 in the tumor microenvironment is known to suppress tumor growth and progression. Here the authors show that PRSS2 represses Tsp-1 by binding to lipoprotein receptor-related protein 1 and suggest targeting PRSS2 mediated Tsp-1 repression as a potential therapeutic strategy.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
DOI：
10.1083/jcb.138.3.707
发表时间：
1997-08-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dawson DW;Pearce SF;Zhong R;Silverstein RL;Frazier WA;Bouck NP
通讯作者：
Bouck NP
影响因子：
5.6
作者：
Greenaway, James;Lawler, Jack;Petrik, Jim
通讯作者：
Petrik, Jim
影响因子：
4.6
作者：
Krüger K;Wik E;Knutsvik G;Nalwoga H;Klingen TA;Arnes JB;Chen Y;Mannelqvist M;Dimitrakopoulou K;Stefansson IM;Birkeland E;Aas T;Tobin NP;Jonassen I;Bergh J;Foulkes WD;Akslen LA
通讯作者：
Akslen LA
影响因子：
28.2
作者：
Catena R;Bhattacharya N;El Rayes T;Wang S;Choi H;Gao D;Ryu S;Joshi N;Bielenberg D;Lee SB;Haukaas SA;Gravdal K;Halvorsen OJ;Akslen LA;Watnick RS;Mittal V
通讯作者：
Mittal V