Serine protease inhibitor Kazal type 1 (SPINK1) drives proliferation and anoikis resistance in a subset of ovarian cancers

被引：24

作者：

Mehner, Christine ^{[1
]}

Oberg, Ann L. ^{[2
]}

Kalli, Kimberly R. ^{[3
]}

Nassar, Aziza ^{[4
]}

Hockla, Alexandra ^{[1
]}

Pendlebury, Devon ^{[1
]}

Cichon, Magdalena A. ^{[1
]}

Goergen, Krista M. ^{[2
]}

Maurer, Matthew J. ^{[2
]}

Goode, Ellen L. ^{[5
]}

Keeney, Gary L. ^{[6
]}

Jatoi, Aminah ^{[3
]}

Sahin-Toth, Miklos ^{[7
]}

Copland, John A. ^{[1
]}

Radisky, Derek C. ^{[1
]}

Radisky, Evette S. ^{[1
]}

机构：

[1] Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA

[2] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA

[3] Mayo Clin, Dept Med Oncol, Rochester, MN USA

[4] Mayo Clin, Dept Lab Med & Pathol, Jacksonville, FL 32224 USA

[5] Mayo Clin, Dept Hlth Sci, Div Epidemiol, Rochester, MN USA

[6] Mayo Clin, Dept Lab Med & Pathol, Div Anat Pathol, Rochester, MN USA

[7] Boston Univ, Dept Mol & Cell Biol, Henry M Goldman Sch Dent Med, Boston, MA 02215 USA

来源：

ONCOTARGET | 2015年 / 6卷 / 34期

关键词：

SPINK1; ovarian cancer; serine protease inhibitor; EGFR; anoikis; TUMOR-ASSOCIATED TRYPSIN; EPIDERMAL-GROWTH-FACTOR; NEGATIVE PROSTATE CANCERS; CRYSTAL-STRUCTURE; DOWN-REGULATION; CYST FLUID; EXPRESSION; TISSUE; TATI; RECEPTOR;

D O I：

10.18632/oncotarget.5927

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ovarian cancer represents the most lethal tumor type among malignancies of the female reproductive system. Overall survival rates remain low. In this study, we identify the serine protease inhibitor Kazal type 1 (SPINK1) as a potential therapeutic target for a subset of ovarian cancers. We show that SPINK1 drives ovarian cancer cell proliferation through activation of epidermal growth factor receptor (EGFR) signaling, and that SPINK1 promotes resistance to anoikis through a distinct mechanism involving protease inhibition. In analyses of ovarian tumor specimens from a Mayo Clinic cohort of 490 patients, we further find that SPINK1 immunostaining represents an independent prognostic factor for poor survival, with the strongest association in patients with nonserous histological tumor subtypes (endometrioid, clear cell, and mucinous). This study provides novel insight into the fundamental processes underlying ovarian cancer progression, and also suggests new avenues for development of molecularly targeted therapies.

引用

页码：35737 / 35754

页数：18

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