Abstract
Rab1A expression is associated with malignant phenotypes in several human tumors; however, the role of Rab1A in lung cancer is still unclear. In this study, we attempted to establish the role of Rab1A in major human lung cancer subtypes. Rab1A expression in different histological types of human lung cancer was analyzed in lung cancer tissues with paired adjacent noncancerous tissues and a large panel of lung cancer cell lines. The effect of Rab1A expression on multiple cancer-associated signaling pathways was also examined. The results demonstrated that Rab1A was significantly overexpressed in the different histological types of lung cancer as compared to non-cancerous tissues, and Rab1A expression was correlated with tumor volume and stage. In a large panel of lung cancer cell lines, high Rab1A expression was observed as compared to a normal lung/bronchus epithelial cell line. However, Rab1A protein levels were not correlated with mTORC1 (P-S6K1), mTORC2 (P-AKT), MEK (P-ERK), JNK (P-c-Jun) or p38MAPK (P-MK2) signaling. Rab1A knockdown had no effect on mTOR signaling or cell growth. These data suggested that Rab1A may be involved in the pathogenesis of human lung cancer in an mTOR- and MAPK-independent manner.
Highlights
Lung cancer is the leading cause of cancer-related death worldwide, with 1.8 million new cases and 1.6 million deaths reported in 2012 [1,2,3]
The results demonstrated that Rab1A was significantly overexpressed in the different histological types of lung cancer as compared to non-cancerous tissues, and Rab1A expression was correlated with tumor volume and stage
Because Rab1A has been reported to be correlated with hyperactive mTORC1 signaling in human colorectal cancer [8], we examined whether Rab1A expression was correlated with mTORC1 signaling in lung cancer
Summary
Lung cancer is the leading cause of cancer-related death worldwide, with 1.8 million new cases and 1.6 million deaths reported in 2012 [1,2,3]. The identification of novel therapeutic targets to improve survival of lung cancer patients is urgently needed. Rab1A, a small GTPase, has been well established to mediate vesicular trafficking between the endoplasmic reticulum (ER) and Golgi apparatus [5]. It is a highly conserved protein, which has been identified in 158 different organisms, ranging from yeast to humans [6, 7]. Overexpression of Rab1A is correlated with a poor prognosis and has been proposed to promote tumor progression by activating the mTORC1 signaling pathway in CRC and HCC, indicating that Rab1A might be a valuable therapeutic target for personalized therapy [8]. We investigated Rab1A expression in tissues and cell lines from different lung cancer subtypes, and assessed the relationships between Rab1A expression and clinical parameters as well as key cancer cell signaling pathways
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