Abstract
To establish treatments to improve the prognosis of cancer patients, it is necessary to find new targets to control metastasis. We found that expression of FilaminC (FLNC), a member of the actin binding and cross-linking filamin protein family is correlated with lymphatic invasion and lymphatic metastasis in esophageal squamous cell carcinoma (ESCC) by increasing cell motility through activation of Rho GTPase.Immunohistochemistry analysis showed that FLNC expression in ESCC is associated with lymphatic invasion, metastasis, and prognosis. FLNC knockdown in esophageal cancer cell lines decreased cell migration in wound healing and transwell migration assays, and invasion in transwell migration assays. Furthermore, FLNC knockdown reduced the amount of activated Rac-1 (GTP-Rac1) and activated Cdc42 (GTP-Cdc42). Our results suggest that FLNC expression is a useful biomarker of ESCC metastatic tendency and that inhibiting FLNC function may be useful to control the metastasis of ESCC.
Highlights
Invasion and metastasis are fundamental characters of cancer [1, 2]
Given that Rho GTPase plays an important role in cell motility and the actin filament system, we examined the role of Rho GTPase in esophageal squamous cell carcinoma (ESCC) to elucidate how filamin C (FLNC) promotes cell motility
To determine whether the expression of FLNC protein is associated with ESCC patient prognosis, we examined 75 cases of advanced ESCC without superficial carcinoma (Table 1)
Summary
Invasion and metastasis are fundamental characters of cancer [1, 2]. The TNM classification of the International Union Against Cancer lists the major prognostic factors in cancer as tumor volume, depth of invasion, and presence of metastasis in lymph nodes or in distant organs [3]. Cancer therapies focus on cancer cell invasion and mechanism of metastasis. The ability of cancer cells to migrate is an important element of cancer invasion and metastasis. Cell migration is an actin-dependent process, involving the polymerization, de-polymerization, branching, and crosslinking of actin filaments [4]. Filamins are a family of actin binding and cross-linking proteins, originally extracted from chicken gizzard muscle [5]. FLNA and FLNB are widely expressed in human tissues while FLNC is restrictively expressed in skeletal and cardiac muscle [7]. All three filamins cross-link actin filaments into three-dimensional structures, and link them to cellular membranes allowing them to serve as scaffolds for transmembrane receptors, channels, signaling molecules, and transcription factors [8, 9]
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