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Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases metastatic potential of prostate cancer cells.

Chatterji T, Varkaris AS, Parikh NU, Song JH, Cheng CJ, Schweppe RE, Alexander S, Davis JW, Troncoso P, Friedl P, Kuang J, Lin SH, Gallick GE - Oncotarget (2015)

Bottom Line: In human specimens, Yes expression was increased in lymph node metastases relative to paired primary tumors from the same patient, and increased pFAK Y861 expression in lymph node metastases correlated with poor prognosis.These results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis.Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

ABSTRACT
To study the role of FAK signaling complexes in promoting metastatic properties of prostate cancer (PCa) cells, we selected stable, highly migratory variants, termed PC3 Mig-3 and DU145 Mig-3, from two well-characterized PCa cell lines, PC3 and DU145. These variants were not only increased migration and invasion in vitro, but were also more metastatic to lymph nodes following intraprostatic injection into nude mice. Both PC3 Mig-3 and DU145 Mig-3 were specifically increased in phosphorylation of FAK Y861. We therefore examined potential alterations in Src family kinases responsible for FAK phosphorylation and determined only Yes expression was increased. Overexpression of Yes in PC3 parental cells and src-/-fyn-/-yes-/- fibroblasts selectively increased FAK Y861 phosphorylation, and increased migration. Knockdown of Yes in PC3 Mig-3 cells decreased migration and decreased lymph node metastasis following orthotopic implantation of into nude mice. In human specimens, Yes expression was increased in lymph node metastases relative to paired primary tumors from the same patient, and increased pFAK Y861 expression in lymph node metastases correlated with poor prognosis. These results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis. Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis.

No MeSH data available.


Related in: MedlinePlus

Migratory variants of PCa cells have increased phosphorylation of FAK Y861A. Expression of FAK and phosphorylation of individual FAK tyrosine sites on indicated cell lysates was determined by immunoblotting (left panel). Quantification (right panel). B. Identical analyses were performed in DU145 cells; immunoblot (left panel); quantification (right panel).
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Figure 2: Migratory variants of PCa cells have increased phosphorylation of FAK Y861A. Expression of FAK and phosphorylation of individual FAK tyrosine sites on indicated cell lysates was determined by immunoblotting (left panel). Quantification (right panel). B. Identical analyses were performed in DU145 cells; immunoblot (left panel); quantification (right panel).

Mentions: Having established two isogenic models with increased migratory potential, we next assessed potential alterations in FAK. FAK expression and tyrosine phosphorylation at each site were determined. Expression of total FAK protein in PC3 Mig-3 (Fig. 2A) (immunoblot, left panel) and DU145 Mig-3 cells (Fig. 2B) (immunoblot, left panel) relative to the parental cells was similar. Phosphorylation of FAK Y397 (the autophosphorylation site) was not changed. However, phosphorylation of one of the SFK-dependent tyrosine sites, FAK Y861, increased with each cycle of migration selection in both PC3-P (Fig. 2A, immunoblots left panel; quantification right panel) and DU145-P cell lines (Fig. 2B, immunoblots left panel; quantification right panel), with no increase in other SFK-dependent tyrosine phosphorylation sites, i.e., FAK Y401, FAK Y577, FAK Y576 and FAK Y925.


Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases metastatic potential of prostate cancer cells.

Chatterji T, Varkaris AS, Parikh NU, Song JH, Cheng CJ, Schweppe RE, Alexander S, Davis JW, Troncoso P, Friedl P, Kuang J, Lin SH, Gallick GE - Oncotarget (2015)

Migratory variants of PCa cells have increased phosphorylation of FAK Y861A. Expression of FAK and phosphorylation of individual FAK tyrosine sites on indicated cell lysates was determined by immunoblotting (left panel). Quantification (right panel). B. Identical analyses were performed in DU145 cells; immunoblot (left panel); quantification (right panel).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496348&req=5

Figure 2: Migratory variants of PCa cells have increased phosphorylation of FAK Y861A. Expression of FAK and phosphorylation of individual FAK tyrosine sites on indicated cell lysates was determined by immunoblotting (left panel). Quantification (right panel). B. Identical analyses were performed in DU145 cells; immunoblot (left panel); quantification (right panel).
Mentions: Having established two isogenic models with increased migratory potential, we next assessed potential alterations in FAK. FAK expression and tyrosine phosphorylation at each site were determined. Expression of total FAK protein in PC3 Mig-3 (Fig. 2A) (immunoblot, left panel) and DU145 Mig-3 cells (Fig. 2B) (immunoblot, left panel) relative to the parental cells was similar. Phosphorylation of FAK Y397 (the autophosphorylation site) was not changed. However, phosphorylation of one of the SFK-dependent tyrosine sites, FAK Y861, increased with each cycle of migration selection in both PC3-P (Fig. 2A, immunoblots left panel; quantification right panel) and DU145-P cell lines (Fig. 2B, immunoblots left panel; quantification right panel), with no increase in other SFK-dependent tyrosine phosphorylation sites, i.e., FAK Y401, FAK Y577, FAK Y576 and FAK Y925.

Bottom Line: In human specimens, Yes expression was increased in lymph node metastases relative to paired primary tumors from the same patient, and increased pFAK Y861 expression in lymph node metastases correlated with poor prognosis.These results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis.Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Genitourinary Medical Oncology, The David Koch Center for Applied Research in Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

ABSTRACT
To study the role of FAK signaling complexes in promoting metastatic properties of prostate cancer (PCa) cells, we selected stable, highly migratory variants, termed PC3 Mig-3 and DU145 Mig-3, from two well-characterized PCa cell lines, PC3 and DU145. These variants were not only increased migration and invasion in vitro, but were also more metastatic to lymph nodes following intraprostatic injection into nude mice. Both PC3 Mig-3 and DU145 Mig-3 were specifically increased in phosphorylation of FAK Y861. We therefore examined potential alterations in Src family kinases responsible for FAK phosphorylation and determined only Yes expression was increased. Overexpression of Yes in PC3 parental cells and src-/-fyn-/-yes-/- fibroblasts selectively increased FAK Y861 phosphorylation, and increased migration. Knockdown of Yes in PC3 Mig-3 cells decreased migration and decreased lymph node metastasis following orthotopic implantation of into nude mice. In human specimens, Yes expression was increased in lymph node metastases relative to paired primary tumors from the same patient, and increased pFAK Y861 expression in lymph node metastases correlated with poor prognosis. These results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis. Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis.

No MeSH data available.


Related in: MedlinePlus