Low expression of SHP-2 is associated with less favorable prostate cancer outcomes

Abstract

Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) is an important regulator of cell signaling because of its ability to dephosphorylate receptors of growth factors as well as the cytokines and tyrosine-phosphorylated proteins associated with these receptors. In the current study, we used four different prostate cancer cell lines: PC3, DU145, LNCaP and LNCaP-IL6+. Tumor specimens from 122 patients with prostate cancer were analyzed using a tissue microarray. Our data demonstrate that all four prostate cancer cell lines express the SHP-2 protein. Additionally, low staining intensity and SHP-2 expression in the cytoplasm of cancer cells in prostate tumor specimens was inversely correlated with prostate volume (p=0.041 and p=0.042, respectively) whereas nuclear staining was positively correlated with extracapsular extension (ece) (p=0.039). In our post-prostatectomy specimens, we found that patients with low SHP-2 expression had less-favorable outcomes with respect to biochemical recurrence (BCR) and clinical progression (p=0.005 and p=0.018 respectively). The loss of cytoplasmic SHP-2 expression is associated with increased growth and prostatic cancer progression.

Src Homology Domain 2-containing Protein-tyrosine Phosphatase-1 (SHP-1) Binds and Dephosphorylates Gα-interacting, Vesicle-associated Protein (GIV)/Girdin and Attenuates the GIV-Phosphatidylinositol 3-Kinase (PI3K)-Akt Signaling Pathway

“…GIV mRNA and protein increase during cancer progression (2,3,12)), and GIV is essential for tumor cell invasion and neoangiogenesis (3,4), whereas expression of SHP-1 is suppressed during cancer progression, and SHP-1 is known to inhibit angiogenesis (57)(58)(59)(60)(61)(62). Because the role of GIV-dependent PI3K-Akt enhancement and cell migration extends beyond tumor cell invasion/metastasis into other diverse biological processes, e.g.…”

PBX3 is a putative biomarker of aggressive prostate cancer

“…The radical prostatectomy cohort from Oslo University Hospital (RP1) included 115 patients laparoscopically operated at Aker University Hospital (presently Oslo University Hospital, Aker) in 2004. The RP2 cohort from Skåne University Hospital consists of 122 patients with localized prostate cancer operated in Malmö between 1998 and 2003, as described previously . In the androgen deprivation therapy (ADT) cohort, 61 patients treated with TUR‐P and ADT at Oslo University Hospital in the period 1992–2008 were identified retrospectively from medical records as described previously .…”

“…Alphelys). The construction of the TMA from Skåne University Hospital has been described previously . In short, areas representing malignant and benign tissues were marked on hematoxylin/eosin stained sections and two cores of 1.0 mm were transferred to a TMA block using a manual arraying device (MTA‐1 Beecher Instruments Inc.).…”

“…The RP2 cohort from Skåne University Hospital consists of 122 patients with localized prostate cancer operated in Malm€ o between 1998 and 2003, as described previously. 20 In the androgen deprivation therapy (ADT) cohort, 61 patients treated with TUR-P and ADT at Oslo University Hospital in the period 1992-2008 were identified retrospectively from medical records as described previously. 21 The 20 patients included in the prostate cancer specific mortality (PCSM) stratified cohort were identified retrospectively from medical records based on the criteria that they either had died from prostate cancer (nine patients) or were alive 10 years post diagnosis (11 patients).…”

Cytotoxic activity of Shp2 inhibitor fumosorinone in human cancer cells

“…There are several conflicting reports on the association between Shp2 and cancer. Certain studies have found that the expression of Shp2 decreases in certain types of tumor (8)(9)(10). However, the opposite was concluded in hepatocellular carcinoma (11)(12)(13).…”