Filamin A: Insights into its Exact Role in Cancers

Abstract

Filamin A (FlnA) is a well-known actin cross-linking protein. It serves as a scaffold for over 90 binding partners and involves in multiple cell functions, of which cell migration and adhesion is especially critical. Recently, its role in the cell has come under scrutiny for FlnA's involvement in cancer development. Originally revealed as a cancer-promoting protein, FlnA actually plays a dual role in cancers. When localized to the cytoplasm, FlnA has a tumor-promoting effect by interacting with signaling molecules. While once localized to the nucleus, it may act to suppress tumor growth and inhibit metastasis by interacting with transcription factors. Thus drugs that can cause FlnA to transpose from cytoplasm to nucleus could be a promising treatment for cancers. Study to this end is on the way in prostate cancer and the results are encouraging. FlnA has been studied in large categories of cancers, such as prostate cancer, breast cancer, melanoma, lung cancer, etc. However, most studies did not evaluate the differences that arise from the localization of the protein, which was a great pity! What's more, although FlnA's is undoubtedly important in cancer invasion and metastasis, both preclinical and clinical researches are very rare in some highly metastatic cancers, such as pancreatic cancer. In this mini-review, we give a comprehensive summary of FlnA' s expression in cancers. Where available, we also indicate the correlation of FlnA with cancer stages and patient prognosis, and clarify its localization (nucleus/cytoplasm) and its dual role (promote/suppress) in different cancers.

Prostate-specific membrane antigen (PSMA) assembles a macromolecular complex regulating growth and survival of prostate cancer cells “in vitro” and correlating with progression “in vivo”

“…Cytoplasmic FLNa has a cancer-promoting activity due to multiple interactions with signalling proteins. In agreement with the expression and the cytoplasmic localization of FLNa in PCa cells FLNa itself has been reported to increase and correlate with an invasive phenotype [19, 20]. By contrast, nuclear FLNa has been shown to suppress cancer growth by interacting with transcription factors [20, 21].…”

Filamin A expression predicts early recurrence of hepatocellular carcinoma after hepatectomy

“…FLNA interacts with signalling molecules and membrane receptors involved in signal transduction to the actin cytoskeleton . It has been shown to play a crucial role in the progression of prostate and ovarian cancers . In addition, Ai et al and Qi et al recently achieved similar results in HCC cell lines and human HCC samples; this research merits further investigations.…”

ATPR‐induced G0/G1 phase arrest in gastric cancer cells by regulating the binding of 14‐3‐3ε and filamin A

“…If filamin A undergoes proteolysis, the C‐terminal fragment is localized to the nucleus and acts to inhibit tumor growth. Although it has been localized in the nucleus, it may play a role in suppressing tumor growth and in decreasing the invasiveness of cancer by interacting with transcription factors . Thus, the induction of filamin A translocating from the cytoplasm to the nucleus may be a promising strategy for cancer treatment.…”