ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

Yuan, Ta Chun; Lin, Fen Fen; Veeramani, Suresh; Chen, S. J.; Earp, H. Shelton; Lin, Ming‐Fong

doi:10.1038/sj.onc.1210570

Cited by 24 publications

(33 citation statements)

References 31 publications

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“…Importantly, PYK2 can promote AR activity in an androgenindependent manner. Similarly, compared with LNCaP C-33 cells expressing a low level of PYK2, LNCaP C-81 cells containing high PYK2 expression exhibit an elevated level of secreted PSA and a rapid growth rate under an androgen-depleted condition (Lee et al 2003, Yuan et al 2007. Although our data suggested the oncogenic role of PYK2 in promoting AR function and PCa cell growth, a previous study showed the inhibitory role of PYK2 in suppressing AR activity in PCa cells by phosphorylating ARA55 .…”

Section: :8contrasting

confidence: 49%

“…In breast cancer cells, the kinase activity of PYK2 and its Y402 phosphorylation are required for cell invasion (Zrihan-Licht et al 2000). In PCa cells, PYK2 can mediate ErbB-2 signaling to upregulate the adhesive ability of AR-positive PCa cells (Yuan et al 2007). PYK2 is also involved in RhoC-promoted invasiveness of PCa cells (Iiizumi et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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PYK2 via S6K1 regulates the function of androgen receptors and the growth of prostate cancer cells

Hsiao¹,

Huang²,

Hung³

et al. 2016

Endocrine-Related Cancer

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Androgen receptor (AR) is a steroid hormone receptor that functions as a transcription factor for regulating cell growth and survival. Aberrant AR function becomes a risk factor for promoting the progression of prostate cancer (PCa). In this study, we examined the roles of proline-rich tyrosine kinase 2 (PYK2) and ribosomal S6 kinase 1 (S6K1) in regulating AR expression and activity and growth properties in PCa cells. Compared with normal prostate tissues, PCa tumors exhibited high levels of PYK2 and S6K1 expression. Furthermore, the expression levels of PYK2 and S6K1 were significantly correlated with nuclear AR expression in PCa tissues. We further found the association between PYK2, S6K1, and AR in their protein expression and phosphorylation levels among normal prostate PZ-HPV-7 cells and prostate cancer LNCaP and 22Rv1 cells. Overexpression of the wild-type PYK2 in PZ-HPV-7 and LNCaP cells promoted AR and S6K1 expression and phosphorylation as well as enhanced cell growth. In contrast, expression of the mutated PYK2 or knockdown of PYK2 expression in LNCaP or 22Rv1 cells caused reduced expression or phosphorylation of AR and S6K1 as well as retarded cell growth. Under an androgen-deprived condition, PYK2-promoted AR expression and phosphorylation and PSA production in LNCaP cells can be abolished by knocking down S6K1 expression. In summary, our data suggested that PYK2 via S6K1 activation modulated AR function and growth properties in PCa cells. Thus, PYK2 and S6K1 may potentially serve as therapeutic targets for PCa treatment.

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Section: :8contrasting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

PYK2 via S6K1 regulates the function of androgen receptors and the growth of prostate cancer cells

Hsiao¹,

Huang²,

Hung³

et al. 2016

Endocrine-Related Cancer

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“…20 For immunoblotting, an aliquot of total cell lysates in an SDS-PAGE sample buffer was electrophoresed and transferred to a nitrocellulose membrane. After blocking with 5% non-fat milk or BSA in Tris-buffered saline containing 0.1% Tween-20 for 1 h at room temperature (RT), the membrane was incubated with the primary antibodies for 3 h at RT or overnight at 4°C.…”

Section: Cell Lysis and Immunoblottingmentioning

confidence: 99%

Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells

Yuan

2016

Laboratory Investigation

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Oral squamous cell carcinoma (OSCC) is a common cancer worldwide. Despite advances in diagnosis and therapy, treatment options for patients with metastatic OSCC are few, due in part to the limited understanding of the molecular events involved in the invasion and metastasis of OSCC. In this study, we investigated the expression of focal adhesion kinase (FAK) and its tyrosine 397 phosphorylation (pY397) in the tissue specimens of OSCC. The roles of pY397 in regulating the activities of Rac1 and cortactin and the invasive properties of OSCC cells were further determined. Results from immunohistochemical analyses in 9 benign, 19 premalignant, and 19 malignant oral tissues showed that the immunoreactivity of FAK was observed in 5 benign (56%), 19 premalignant (100%), and 18 malignant tissues (95%), whereas the immunoreactivity of pY397 was only found in 1 of 9 (11%) benign lesions but was observed in 9 premalignant (47%) and 12 malignant (63%) lesions. Compared with the low-invading SCC4 cells, the high-invading OECM-1 cells exhibited higher levels of FAK expression and pY397, correlating with higher levels of GTP-bound Rac1 and cortactin phosphorylation. Manipulation of FAK expression or Y397 phosphorylation in SCC4, FaDu, OECM-1, or HSC-3 cells regulated their Rac1 activities and invasive properties. Furthermore, treatment of NSC23766, a Rac1-specific inhibitor, in OECM-1 and HSC-3 cells led to reduced invasive properties. Nevertheless, knockdown of FAK expression or suppression of pY397 had no effect on the cortactin activity in OECM-1 cells. The data collectively suggest that pY397 plays critical roles in the FAK-promoted Rac1 activation and invasive properties in OSCC cells. Thus, the inhibition of FAK phosphorylation at Y397 or Rac1 activity can serve as a therapeutic strategy for treating patients with metastatic OSCC. Oral squamous cell carcinoma (OSCC) is the most common malignancy occurring in the oral cavity that usually arises from the buccal mucosa and tongue. During the tumor progression, OSCC cells gradually spread and invade to neighboring tissues, including the nasal cavity or the maxillary facial structures, and eventually metastasize to neck lymph nodes and distant organs. 1 Similar to other malignant diseases, tumor metastasis is a great challenge for the treatment of OSCC. This notion is supported by the fact that only 50% of diagnosed OSCC patients can survive for 5 years, and this is mainly because OSCC patients continue to die from tumor relapse at regional or distant sites. 2 Despite advances in diagnosis and therapy in past decades, the promising strategy for treating patients with metastatic OSCC is still underdeveloped, due in part to the limited understanding of the molecular events involved in invasion and metastasis of OSCC. The underlying molecular basis of OSCC metastasis deserves intensive study.Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase and functionally involves the regulatory processes of multiple cellular events, including adhesion, migration, invasion, prolifer...

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“…The cells were harvested, and the cell lysates were prepared as described previously (Yuan et al 2007). For immunoblotting, an aliquot of total cell lysates in an SDS-PAGE sample buffer was separated by electrophoresis and then transferred to a nitrocellulose membrane.…”

Section: Cell Lysis and Immunoblottingmentioning

confidence: 99%

Regulation of estrogen receptor α function in oral squamous cell carcinoma cells by FAK signaling

Chang¹,

Hsu²,

Wu³

et al. 2014

Endocrine-Related Cancer

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Estrogen receptor a (ERA) is a DNA-binding transcription factor that plays an important role in the regulation of cell growth. Previous studies indicated that the expression of ERa in cell lines and tumors derived from oral squamous cell carcinoma (OSCC). The aim of this study was to examine the activity and function of ERa in OSCC cells and the mechanism underlying ERa activation. Immunochemical analyses in benign (nZ11) and malignant (nZ21) lesions of the oral cavity showed that ERa immunoreactivity was observed in 43% (9/21) of malignant lesions, whereas none of benign lesions showed ERa immunoreactivity. The ERa expression was also found in three OSCC cell lines and its transcriptional activity was correlated with cell growth. Addition of estradiol stimulated cell growth, whereas treatment of tamoxifen or knockdown of ERa expression caused reduced cell growth. Interestingly, the expression and activity of focal adhesion kinase (FAK) were associated with the phosphorylation of ERa at serine 118 in OSCC cells. Elevated expression of FAK in the slow-growing SCC25 cells caused increases in ERa phosphorylation, transcriptional activity, and cell growth rate, whereas knockdown of FAK expression in the rapid-growing OECM-1 cells led to reduced ERa phosphorylation and activity and retarded cell growth. Inhibition of the activity of protein kinase B (AKT), but not ERK, abolished FAK-promoted ERa phosphorylation. These results suggest that OSCC cells expressed functional ERa, whose activity can be enhanced by FAK/AKT signaling, and this was critical for promoting cell growth. Thus, FAK and ERa can serve as the therapeutic targets for the treatment of OSCC. Key Words" oral squamous cell carcinoma " estrogen receptor a " focal adhesion kinase

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ErbB-2 via PYK2 upregulates the adhesive ability of androgen receptor-positive human prostate cancer cells

Cited by 24 publications

References 31 publications

PYK2 via S6K1 regulates the function of androgen receptors and the growth of prostate cancer cells

PYK2 via S6K1 regulates the function of androgen receptors and the growth of prostate cancer cells

Tyrosine 397 phosphorylation is critical for FAK-promoted Rac1 activation and invasive properties in oral squamous cell carcinoma cells

Regulation of estrogen receptor α function in oral squamous cell carcinoma cells by FAK signaling

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