M1832 Autophagy Mediated By VMP1 Expression Is a Survival Mechanism in Caerulein-Treated AR42J Pancreas Cells

Sacchetti, Maria Luisa; Grasso, Daniel; Ré, Andrea E. Lo; Pardo, Romina Paola; Iovanna, Juan; Ropolo, Alejandro; Vaccaro, María I.

doi:10.1016/s0016-5085(08)62004-1

Cited by 1 publication

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“…Vmp1 has been associated with different functions including autophagy and cell adhesion, while there are still uncertainties in its underlying mechanism of tumor suppression, whether it is functioning in autophagy (when present in the ER) or in cell adhesion (when located in the plasma membrane). Autophagy has recently emerged as a key regulator of multiple aspects of cancer biology and autophagy deficiency leads to tumorigenesis in the liver .…”

Section: Discussionmentioning

confidence: 99%

“…(25) The overexpressed human Vmp1 was reported to localize in the endoplasmic reticulum (ER) and Golgi complex, (26) where it appeared to be required for protein secretion and Golgi organization, (11) as well as organelle biogenesis and multicellular development. (27) Besides its different functions including membrane traffic, (13) growth (12) and autophagy, (14,15,28,29) interestingly, recent reports showed that Vmp1 was located in the plasma membrane playing a critical role in cell-cell contact. (18,23,24) These results suggest a role for Vmp1 in tumor relevant cellular processes, which is further supported by expression profiling data.…”

Section: Discussionmentioning

confidence: 99%

“…As ZO-1 plays an important role in cancer-related cell biological systems, (35,36) Vmp1's direct interaction with ZO-1 might provide some evidence on the phenomenon that Vmp1 controls HCC behaviors thorough regulation of cell-cell contacts. Vmp1 has been associated with different functions including autophagy (14,15,28,29) and cell adhesion, (18,23,24) while there are still uncertainties in its underlying mechanism of tumor suppression, whether it is functioning in autophagy (when present in the ER) or in cell adhesion (when located in the plasma membrane). Autophagy has recently emerged as a key regulator of multiple aspects of cancer biology (37) and autophagy deficiency leads to tumorigenesis in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…It has previously been reported that the overexpressed protein is an inhibitor of cell proliferation, anchorage‐independent growth and secretory membrane transport . Moreover, recent studies have demonstrated that Vmp1 is necessary in autophagy and its expression induces the formation of autophagosomes . Interestingly, the expression profiling on a cDNA array and another complementary DNA microarray revealed that VMP1 was downregulated in renal cell carcinoma .…”

mentioning

confidence: 98%

“…(13) Moreover, recent studies have demonstrated that Vmp1 is necessary in autophagy and its expression induces the formation of autophagosomes. (14,15) Interestingly, the expression profiling on a cDNA array and another complementary DNA microarray revealed that VMP1 was downregulated in renal cell carcinoma. (16,17) Furthermore, Vmp1 is an essential component of initial cell-cell contacts and tight junction formation where it colocalizes with zonula occludens-1 (ZO-1) in spots between neighboring cells.…”

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confidence: 99%

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Novel roles of Vmp1: Inhibition metastasis and proliferation of hepatocellular carcinoma

et al. 2012

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Hepatocellular carcinoma (HCC) is one of the most deadly human cancers because of its high incidence of metastasis. Despite extensive efforts, therapies against metastasis of HCC remain underdeveloped. Vacuole membrane protein 1 (Vmp1) was recently identified to be involved in cancer-relevant processes; however, its expression, clinical significance and biological function in HCC progression are still unknown. Therefore, we evaluated the expression of Vmp1 in human HCC specimens. To functionally characterize Vmp1 in HCC, we upregulated its expression in HCCLM3 cells using a plasmid transfection approach, following which both in vitro and in vivo models were used to elucidate its role. A significant downregulation of Vmp1 was found in human HCC tissues and closely correlated with multiple tumor nodes, absence of capsular formation, vein invasion and poor prognosis of HCC. Such expression was verified with HCC cell lines including HepG2, MHCC97-L and HCCLM3, and the Vmp1 expression levels negatively correlated with metastatic potential. Interestingly, upregulation of Vmp1 significantly affects proliferation, migration, invasion and adhesion of HCCLM3 cells. Using a mouse model, we demonstrated that upregulation of Vmp1 was associated with suppression of growth and pulmonary metastases of HCC. Therefore, our data suggest Vmp1 is a novel prognostic marker and potential therapeutic target for metastasis of HCC. (Cancer Sci 2012; 103: 2110-2119 H epatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of death from cancer, resulting in more than 600 000 deaths per year.(1,2) During the past decade, the long-term survival rate remains unsatisfactory because of a high incidence of recurrence and metastasis after hepatic resection, with a 5-year actuarial recurrence rate of 75-100% reported in the literature.(3) To predict recurrence, metastasis and prognosis in patients with HCC after hepatic resection is a clinical issue of great significance. Various prognostic markers of HCC have been identified, such as vascular endothelial growth factor (VEGF), osteopontin (OPN) and transforming growth factor-b (TGF-b). Based on a genomic analysis, we previously reported ras homologous gene C (RhoC), high mobility group A1 (HGMA1) and Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 (WAVE2) as potential markers for metastasis of HCC.(4-7) All these findings represent significant progress in this field. However, the mechanisms underlying HCC metastasis are still not fully understood, supporting a need for further studies. Thus, exploring new prognostic markers and further inhibition of invasion and metastasis is of great importance in HCC therapies. (8) It is well known that reduced levels of cell-cell adhesion proteins often correlate with tumor invasion and metastasis. (9)

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Section: Discussionmentioning

confidence: 99%