Downregulation of Rab25 activates Akt1 in head and neck squamous cell carcinoma

Abstract

Abstract. Several studies have suggested that Ras-associated binding 25 protein (Rab25) is involved in the pathogenesis of human cancer. Although it has been demonstrated that the development of head and neck squamous cell carcinoma (HNSCC) is the result of an accumulation of multiple sequential genetic and epigenetic alterations in key genes with important functions in cell growth and the cell cycle, recent studies have indicated that HNSCC is a complex and heterogenous disease. To the best of our knowledge, there is no data regarding the regulation of the Rab25 gene at the mRNA or protein level in HNSCC. Furthermore, available data on Rab25 expression in other types of cancer are conflicting. The aim of the present study was to investigate whether Rab25 is involved in the development and/or progression of HNSCC, and to analyze the mechanisms underlying its effects in this type of cancer. The expression of Rab25 mRNA in HNSCC tissues and adjacent non-tumor tissue samples was measured using reverse transcription-quantitative polymerase chain reaction, while the level of the Rab25, Akt1 and phosphorylated-Akt1 proteins was measured using western blotting. Expression of Rab25 mRNA and protein was downregulated in 69.1% and 56.1% of tumor tissue samples, respectively. This downregulation was associated with an increase in p-Akt1 expression, in the absence of a change in total Akt1 protein levels, in tumor tissues compared with normal tissues. The current findings suggest that Rab25 acts as a tumor suppressor in HNSCC.

Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking

“…These data suggested that while Rab25 regulates trafficking in many cells, the actual patterns of integrin regulation are dependent on tumor context. In tumors originating from HNSCC , oral SCC , oropharyngeal SCC, and esophageal SCC , the tumor suppressor effects of Rab25 are well established. This conclusion is supported by a positive prognosis for high Rab25 expression in patients with HNSCC .…”

“…Rab25, a member of the Rab11 small GTPase family, regulates the trafficking of integral membrane proteins (EGFR, α6β1 integrin) and receptors, which are critical to the maintenance of polarity in epithelial cells . As Rab25 is highly expressed in epithelial cells, Rab25 deficiency elicits aggressive behaviors in epithelial cancers, including human colon cancer , triple‐negative breast cancer , and head and neck squamous cell carcinoma (HNSCC) , suggesting that Rab25 may work as a crucial tumor suppressor in epithelial cancers.…”

The Endosomal Recycling Pathway—At the Crossroads of the Cell

“…However, the tumorigenic properties of Rab25 appear to be context-dependent. Loss of Rab25 is common in colorectal cancer and head and neck squamous cell carcinomas, where it appears to act as a tumour suppressor gene [ 71 , 72 ]. It is hypothesised that lack of Rab25 in these highly polarised cell types results in the loss of targeted delivery of cell surface proteins, possibly contributing to dedifferentiation of these cells.…”

Comprehensive Analysis of Expression, Clinicopathological Association and Potential Prognostic Significance of RABs in Pancreatic Cancer

“…Further, the role of RABs in the shedding of extracellular vesicles has also been reported [ 55 , 56 , 57 , 58 ]. Aberrant expression of RABs is reported in various cancers, and they are shown to act either as a tumor promoter or suppressor in a context-dependent manner [ 59 , 60 , 61 , 62 , 63 ].…”