RAB10 overexpression promotes tumor growth and indicates poor prognosis of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC), one of the most common and lethal cancers worldwide, has a high recurrence rate with current treatment modalities. Identifying biomarkers for early diagnosis and discovering new sufficient molecular targets for the development of targeted therapies are urgently needed. RAB10, a member of the RAS family, has been shown to be highly expressed in HCC. However, the function of RAB10 in HCC is less studied. Here we report that RAB10 acts as an oncogene in HCC. The shRNA-mediated knockdown of RAB10 significantly reduced the proliferation of HCC cells and colony formation, induced cell cycle arrest at G0/G1 phase and increased apoptosis in vitro. In addition, RAB10 knockdown suppressed HCC growth in nude mice. Moreover, RAB10 silencing decreased the phosphorylation of InsR, Met/HGFR, Ron/MST1R, Ret, c-Kit/SCFR, EphA3, EphB4, Tyro3/Dtk, Axl, Tie2/TEK, VEGFR2/KDR, Akt/PKB/Rac, S6 Ribosomal Protein and c-Abl, while the phosphorylation of HSP27, p38 MAPK, Chk2 and TAK1 increased significantly. These results suggest that RAB10 regulates cell survival and proliferation through multiple oncogenic, cell stress and apoptosis pathways. More importantly, high RAB10 expression levels in HCC cells correlated with a poor prognosis in HCC patients. Therefore, our findings revealed an oncogenic role for RAB10 in the pathogenesis of HCC and that RAB10 is a potential molecular target or a biomarker for HCC.

Exosomes Derived from Human Primary and Metastatic Colorectal Cancer Cells Contribute to Functional Heterogeneity of Activated Fibroblasts by Reprogramming Their Proteome

“…Elevated expression of IL‐8 was validated in activated neoHFFs using fluorescent microscopy (Figure S4B, Supporting Information). Indeed, both Rab10a and NDRG1 have been shown to promote section of IL‐8 . Cancer cells release Exos that stimulate stromal cells to secrete IL‐8 that, in turn, modulates angiogenesis and leukemia cell survival .…”

Retracted Article: Down-regulation of Rab10 inhibits hypoxia-induced invasion and EMT in thyroid cancer cells by targeting HIF-1α through the PI3K/Akt pathway

“…19,20 Recently, Rab10 has been demonstrated to be aberrantly expressed in some types of cancers and show biological signicance in cancer progression. [21][22][23] However, the specic role of Rab10 in thyroid cancer remains unknown.…”

<p>microRNA-519d Induces Autophagy and Apoptosis of Human Hepatocellular Carcinoma Cells Through Activation of the AMPK Signaling Pathway via Rab10</p>

“…12 Moreover, increased Rab10 expression has been linked to poor prognosis in HCC accompanied by pathological complications such as distant metastasis. 29 Rab10 was also identified as an oncogene due to the evidence that shRNA-mediated knockdown of Rab10 resulted in a reduction of HCC cell proliferation and colony formation. 29 Also, a recent study demonstrated that Rab10 was highly expressed in some liver cancer tissue samples.…”

“…29 Rab10 was also identified as an oncogene due to the evidence that shRNA-mediated knockdown of Rab10 resulted in a reduction of HCC cell proliferation and colony formation. 29 Also, a recent study demonstrated that Rab10 was highly expressed in some liver cancer tissue samples. 30 Furthermore, inhibition of Rab10 repressed osteosarcoma cell proliferation and metastasis, and its expression was negatively regulated by miR-329.…”