Abstract
Rab23 was a member of Ras-related small GTPase family, which played a key role in the regulation of Shh signaling pathway. However, the function and regulatory mechanism of Rab23 in cutaneous squamous cell carcinoma was unknown. In this study, we found that the expression level of Rab23 was higher in moderately to poorly tumor differentiation tissue and non-exposed positions, and no statistically significant difference showed in Rab23 expression according to trauma/chronic disease, location on lips/ears, tumor size, gender, or age. Interestingly, we found that Rab23 RNAi suppressed cell invasion and Rab23 overexpression promoted cell invasion depended on GTP-bound form of Rab23. Inhibition of Rac1 activity or Rac1 silencing with siRNA fragment attenuated Rab23 promoted cells migration and invasion. Notably, we confirmed that Rab23 was co-localized with integrin β1 in cell membrane of Rab23 WT and Rab23 Q68L stable expression cells and Rab23 efficiently coprecipitated with integrin β1 and Tiam1 in a GTP-dependent manner. Further, integrin β1 siRNA interrupted the coprecipitation between Rab23 and Tiam1 and attenuated Rab23 promoted cells migration and invasion. Taken together, our results indicated that Rab23 promotes squamous cell carcinoma cells migration and invasion by regulating Integrin β1/Tiam1/Rac1 pathway.
Highlights
Cutaneous squamous cell carcinoma is the second most common form of non-melanoma skin cancer
We have detailed that Rab23 was upregulated in SCC tissues and cell lines, which strongly promoted migration and invasion of SCC cells, and we found this appears to be mediated by the activation of Rac1 GTPase
We revealed a direct interaction among integrin β1, Rab23 and Tiam1, the direct interaction between Rab23 and Tiam1 was disappeared after integrin β1 siRNA
Summary
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of non-melanoma skin cancer. The five-year rate of recurrence of primary cutaneous lesions is 8 percent, and the fiveyear rate of metastasis is 5 percent. The fatality rate of metastasis cSCC is about 40 percent [1]. In a subset of patients, cSCC can be biologically aggressive, showing a greater propensity for local recurrence and metastasis to regional lymph nodes and distant organs. The percentage of primary cSCCs that metastasize varies between case series but is usually under 5%. In high-risk cSCC, this percentage is higher [5], ranging from 15%(2) to 38%(1), depending on the study. An urgent better understanding of precise molecular mechanisms of metastasis cSCC and more efficacy therapeutic target are needed for improving clinical outcome of this fatal disease
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