Knockdown of protein tyrosine phosphatase SHP-1 inhibits G1/S progression in prostate cancer cells through the regulation of components of the cell-cycle machinery

We have identified the presence of leupaxin (LPXN), which belongs to the paxillin extended family of focal adhesion-associated adaptor proteins, in prostate cancer cells. Previous studies have demonstrated that LPXN is a component of the podosomal signaling complex found in osteoclasts, where LPXN was found to associate with the protein tyrosine kinases Pyk2 and c-Src and the cytosolic protein tyrosine phosphatase-proline-, glutamate-, serine-, and threonine-rich sequence (PTP-PEST). In the current study, LPXN was detectable as a 50-kDa protein in PC-3 cells, a bone-derived metastatic prostate cancer cell line. In PC-3 cells, LPXN was also found to associate with Pyk2, c-Src, and PTP-PEST. A siRNA-mediated inhibition of LPXN resulted in decreased in vitro PC-3 cell migration. A recombinant adenoviral-mediated overexpression of LPXN resulted in an increased association of Pyk2 with LPXN, whereas a similar adenoviral-mediated overexpression of PTP-PEST resulted in decreased association of Pyk2 and c-Src with LPXN. The overexpression of LPXN in PC-3 cells resulted in increased migration, as assessed by in vitro Transwell migration assays. On the contrary, the overexpression of PTP-PEST in PC-3 cells resulted in decreased migration. The overexpression of LPXN resulted in increased activity of Rho GTPase, which was decreased in PTP-PEST-overexpressing cells. The increase in Rho GTPase activity following overexpression of LPXN was inhibited in the presence of Y27632, a selective inhibitor of Rho GTPase. In conclusion, our data demonstrate that LPXN forms a signaling complex with Pyk2, c-Src, and PTP-PEST to regulate migration of prostate cancer cells.

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Cellular prostatic acid phosphatase: a protein tyrosine phosphatase involved in androgen-independent proliferation of prostate cancer

Endocrine Related Cancer ◽

10.1677/erc.1.00950 ◽

2005 ◽

Vol 12 (4) ◽

pp. 805-822 ◽

Cited By ~ 70

Author(s):

Suresh Veeramani ◽

Ta-Chun Yuan ◽

Siu-Ju Chen ◽

Fen-Fen Lin ◽

Juliette E Petersen ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Prostatic Acid Phosphatase ◽

Prostate Cancer Progression ◽

Prostate Cancer Cells ◽

Her 2 ◽

Androgen Independent

Human prostatic acid phosphatase (PAcP) was used as a valuable surrogate marker for monitoring prostate cancer prior to the availability of prostate-specific antigen (PSA). Even though the level of PAcP is increased in the circulation of prostate cancer patients, its intracellular level and activity are greatly diminished in prostate cancer cells. Recent advances in understanding the function of the cellular form of PAcP (cPAcP) have shed some light on its role in prostate carcinogenesis, which may have potential applications for prostate cancer therapy. It is now evident that cPAcP functions as a neutral protein tyrosine phosphatase (PTP) in prostate cancer cells and dephosphorylates HER-2/ErbB-2/Neu (HER-2: human epidermal growth factor receptor-2) at the phosphotyrosine (p-Tyr) residues. Dephosphorylation of HER-2 at its p-Tyr residues results in the down-regulation of its specific activity, which leads to decreases in growth and tumorigenicity of those cancer cells. Conversely, decreased cPAcP expression correlates with hyperphosphorylation of HER-2 at tyrosine residues and activation of downstream extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling, which results in prostate cancer progression as well as androgen-independent growth of prostate cancer cells. These in vitro results on the effect of cPAcP on androgen-independent growth of prostate cancer cells corroborate the clinical findings that cPAcP level is greatly decreased in advanced prostate cancer and provide insights into one of the molecular mechanisms involved in prostate cancer progression. Results from experiments using xenograft animal models further indicate a novel role of cPAcP as a tumor suppressor. Future studies are warranted to clarify the use of cPAcP as a therapeutic agent in human prostate cancer patients.

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Receptor protein tyrosine phosphatase alpha signaling is involved in androgen depletion-induced neuroendocrine differentiation of androgen-sensitive LNCaP human prostate cancer cells

Oncogene ◽

10.1038/sj.onc.1206764 ◽

2003 ◽

Vol 22 (43) ◽

pp. 6704-6716 ◽

Cited By ~ 45

Author(s):

Xiu-Qing Zhang ◽

Dmitry Kondrikov ◽

Ta-Chun Yuan ◽

Fen-Fen Lin ◽

Joel Hansen ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Neuroendocrine Differentiation ◽

Receptor Protein ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Receptor Protein Tyrosine Phosphatase ◽

Androgen Depletion

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Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180209152215 ◽

2019 ◽

Vol 18 (9) ◽

pp. 1313-1322 ◽

Cited By ~ 5

Author(s):

Manjula Devi Ramamoorthy ◽

Ashok Kumar ◽

Mahesh Ayyavu ◽

Kannan Narayanan Dhiraviam

Keyword(s):

Prostate Cancer ◽

Reactive Oxygen Species ◽

Cell Cycle ◽

Membrane Potential ◽

Cancer Cells ◽

Mitochondrial Membrane Potential ◽

Mitochondrial Membrane ◽

Reactive Oxygen ◽

Oxygen Species ◽

Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

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