colon cancer. Fhl2 demonstrates an oncogenic property in colon cancer which induces the differentiation of some in vitro colon cancer models. FHL2 is as well crucial to colon cancer cells invasion, migration and adhesion to extracellular matrix. The expression of FHL2 is positively regulated by transforming growth factor beta 1 (TGF-β1) stimulations which induces epithelial-mesenchymal transition (EMT) and endows cancer cells with metastatic properties. The TGF-β1-midiated alternation of FHL2 expression level might therefore trigger colon cell invasion. Besides, the subcellular localization of FHL2 can be modulated by TGF-β1 in sporadic colon cancer which resulted in the polymerization of alpha smooth muscle actin (α-SMA). This process induces the fibroblast to take up a myofibroblast phenotype and contributes to cancer invasion. FHL2 can also induce EMT and cancer cell migration by affecting the structural integrity of membrane-associated E-cadherin-β-catenin complex. Liver cancer In the most common form liver cancer, the hepatocellular carcinoma (HCC), FHL2 is always downregulated in the clinical samples. Therefore, fhl2 is exhibiting a tumor-suppressive effect on HCC. Similar to p53, overexpression of FHL2 inhibit the proliferative activity of the HCC Hep3B cell line by decreasing its cyclin D1 expression and increasing P21 and P27 expression supporting the time-dependent cellular repair process. Of note, a database of FHL2-regulated genes in murine liver has recently been established by using microarray and bioinformatics analysis, which provide useful information concerning most of the pathways and new genes related to FHL2. Prostate cancer The molecular communication between androgen receptor (AR) and FHL2 is linked to the disease development of prostate cancer such as aggressiveness and biochemical recurrence (i.e., rise in circulatory prostate-specific antigen (PSA) levels after surgical or radiography treatment) FHL2 expression is profoundly initiated by androgen through the mediation of serum response factor (SFR) and the RhoA / actin / megakaryocytic acute leukemia (MAL) signaling axis functioning upstream of SRF. On the other hand, FHL2 is the coactivator of AR and is able to modulate AR signaling by altering the effect of Aryl hydrocarbon receptor (AhR) imposing AR activity with as yet unknown mechanisms. Calpain cleavage of cytoskeletal protein filamin which is increased in prostate cancer could induce the nuclear translocation of FHL2, and this subsequently increase AR coactivation. Interactions FHL2 has been shown to interact with: Androgen receptor, BRCA1, CTNNB1, CD18, CD29, CD49c, CREB1, EIF6, FHL3, IGFBP5, ITGA7, ITGB6, MAPK1, PSEN2, TRAF6, TTN, ZNF638, and ZBTB16. Notes References Further reading External links Transcription