Biomarker: FAK

Histology type: endometrial carcinoma

Country: Germany

Region: Freiburg

Study type: prospective study

Followed up time :

Subgroup 1 name : moderate and strong expressions

Subgroup 1 number: 120

Subgroup 2 name: low overexpression

Subgroup 2 number: 14

Conclusion: Further studies are warranted to elucidate whether FAK expression analysis is a suitable tool in stratifying patients at different risks of disease progress, and wether FAK might become a new molecular target for endometrial anticancer therapy.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : expression

Expression elevation: The resulting IHC score was based exclusively on the intensity of IHC staining.A score was applied to classify the intensity of immunohistochemical (IHC) staining as absent (0), weak (1+), moderate (2+), or strong (3+). The percentage of positive cells for each intensity was estimated for the whole tumor on 1 section. The extent of expression was simplified as focal (when G50% of cells were stained) and diffuse (when 950% of cells were stained).

Statictics: Median;Range

Cohort age: 66;36–94

Funtion Uniprot: Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. Isoform 6 Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.

UniProt ID: Q05397

UniProt Link: https://www.uniprot.org/uniprotkb/Q05397/entry

Biological function from UniProt: #Angiogenesis

Molecular function from UniProt:

Tissue specificity from UniProt: Detected in B and T-lymphocytes. Isoform 1 and isoform 6 are detected in lung fibroblasts (at protein level). Ubiquitous. Expressed in epithelial cells (at protein level) (PubMed:31630787).

Subcellular UniProt: #Cell junction #Cell membrane #Cell projection #Cytoplasm #Cytoskeleton

Alternative name from UniProt:

Catalytic activity: ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]

Activity regulation: Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal kinase activity. Inhibited by TAC544, TAE226, PF-573,228 and PF-562,271

Recommended name: Focal adhesion kinase 1

Gene name from HGNC: PTK2 (FADK, FAK, FAK1, PPP1R71)

HPA class: Cancer-related genes Disease related genes Enzymes Metabolic proteins Plasma proteins Potential drug targets

AlphaFold DB: Q05397

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q05397

Developmental stage: Isoform 6 Detected in cultured cells, immediately after seeding and before formation of focal adhesions (at protein level).

HPA link: https://www.proteinatlas.org/ENSG00000169398-PTK2

Tissue specificity RNA from HPA: Low tissue specificity

Tissue expression from HPA: Cytoplasmic expression in most tissues

Single cell type specificity Cell type enhanced (Oligodendrocytes, Excitatory neurons, Oligodendrocyte precursor cells, Astrocytes)

Immune cell specificity: Low immune cell specificity

Subcellular summary HPA Located in Vesicles, Focal adhesion sites, Cytosol (CCD Transcript)

Cancer prognostic summary HPA Prognostic marker in breast cancer (unfavorable) and endometrial cancer (unfavorable)

Pathology link: https://www.proteinatlas.org/ENSG00000169398-PTK2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000169398-PTK2/pathology/endometrial+cancer

Disease: No disease ID

Note1: Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer

OMIM: 600758

OMIM link2: https://www.omim.org/entry/600758

HGNC ID: HGNC:9611

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9611