Clinical significance FHL2

1 clinical significance

1.1 breast cancer
1.2 gastrointestinal cancer
1.3 liver cancer
1.4 prostate cancer

clinical significance

the expression , functions of fhl2 varies depending on cancer types. appeared phenomenon highly related differential mechanistic transcriptional regulations of fhl2 in various types of cancer. however, participation of fhl2 mutations , posttranslational modifications of fhl2 in carcinogenesis cannot ignored. in fact, functional mutation of fhl2 has been identified in patient familial dilated cardiomyopathy (dcm) , associated pathogenesis. implied fhl2 mutation may profoundly affect diverse cancer progressions. however, records describing effects of fhl2 mutations on carcinogenesis scarce.

phosphorylation of fhl-2 protein has no significant effects on fhl2 functioning both in vitro , in vivo. provided existence of posttranscriptional modifications on fhl2 other phosphorylation still unclear , fhl2 functions exclusively through protein-protein interactions, research works in direction still interested. in particular, mechanisms underpinning subcellular localization of fhl2 should focused. fhl2 can traffic freely between nuclear , different cellular compartments. interacts other proteinaceous binding partners belonging different functional classes including, not limited to, transcription factors , signal transducers. therefore, fhl2 translocation important in regulating different molecular signaling pathways modify carcinogenesis, example, nuclear translocation of fhl2 related aggressiveness , recurrence of prostate cancer similar evidence has been identified in experiment using a7fil+ cells , nih 3t3 cell line disease model.

breast cancer

the fhl2 protein interacts breast cancer type 1 susceptibility gene (brca1) enhances transactivation of brca1. in addition, intratumoral fhl2 level 1 of factors determining worse survival of breast cancer patients

gastrointestinal cancer

fhl2 related gastrointestinal cancers , in particular, colon cancer. fhl2 demonstrates oncogenic property in colon cancer induces differentiation of in vitro colon cancer models. fhl2 crucial colon cancer cells invasion, migration , adhesion extracellular matrix. expression of fhl2 positively regulated transforming growth factor beta 1 (tgf-β1) stimulations induces epithelial-mesenchymal transition (emt) , endows cancer cells metastatic properties. tgf-β1-midiated alternation of fhl2 expression level might therefore trigger colon cell invasion. besides, subcellular localization of fhl2 can modulated tgf-β1 in sporadic colon cancer resulted in polymerization of alpha smooth muscle actin (α-sma). process induces fibroblast take myofibroblast phenotype , contributes cancer invasion. fhl2 can induce emt , cancer cell migration affecting structural integrity of membrane-associated e-cadherin-β-catenin complex.

liver cancer

in common form liver cancer, hepatocellular carcinoma (hcc), fhl2 downregulated in clinical samples. therefore, fhl2 exhibiting tumor-suppressive effect on hcc. similar p53, overexpression of fhl2 inhibit proliferative activity of hcc hep3b cell line decreasing cyclin d1 expression , increasing p21 , p27 expression supporting time-dependent cellular repair process. of note, database of fhl2-regulated genes in murine liver has been established using microarray , bioinformatics analysis, provide useful information concerning of pathways , new genes related fhl2.

prostate cancer

the molecular communication between androgen receptor (ar) , fhl2 linked disease development of prostate cancer such aggressiveness , biochemical recurrence (i.e., rise in circulatory prostate-specific antigen (psa) levels after surgical or radiography treatment) fhl2 expression profoundly initiated androgen through mediation of serum response factor (sfr) , rhoa / actin / megakaryocytic acute leukemia (mal) signaling axis functioning upstream of srf. on other hand, fhl2 coactivator of ar , able modulate ar signaling altering effect of aryl hydrocarbon receptor (ahr) imposing ar activity yet unknown mechanisms. calpain cleavage of cytoskeletal protein filamin increased in prostate cancer induce nuclear translocation of fhl2, , subsequently increase ar coactivation.