Overexpression of OLC1 Promotes Tumorigenesis of Human Esophageal Squamous Cell Carcinoma

Xiao, Li; Suo, Jian; Shao, Shujuan; Xue, Liyan; Chen, Wei; Dong, Lei; Fu, Ming; Lü, Ning; Zhan, Qimin; Tong, Tong

doi:10.1371/journal.pone.0090958

Cited by 8 publications

(8 citation statements)

References 45 publications

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“…Esophageal cancer is difficult to diagnose, and frequently has a poor prognosis. Therefore, it is of importance to identify new candidate markers to facilitate the early diagnosis and treatment of EC (27). KLK10 codes a secreted serine protease, whose physiological function remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Upregulated KLK10 inhibits esophageal cancer proliferation and enhances cisplatin sensitivity in vitro

Fan

et al. 2015

Oncology Reports

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The kallikrein-related peptidase 10 (KLK10) gene has tumor-suppressive function in various types of human cancer. However, previous studies showed that KLK10 also acts as an oncogene and is upregulated in gastrointestinal tumors. The role of KLK10 in human esophageal cancer (EC) remains unclear. In the present study, the expression of KLK10 in human esophageal and non-esophageal cancer tissues was investigated by immunohistochemistry. Quantitative RT-PCR and western blot analysis were utilized to detect KLK10 mRNA and protein expression in human esophageal cancer cell lines (TE-1 and Eca-109). Small interference RNA was utilized to specifically knockdown KLK10 expression in Eca-109 and TE-1 cells. Cell proliferation, cell cycle analysis as well as CDDP-dependent apoptosis were determined using a CCK-8 assay and flow cytometry. The results showed that, KLK10 was positive in 67 out of 83 (80.72%) human EC and positive in 3 out of 11 (27.27%) normal tissues (P=0.001). The present study indicated that KLK10 potentially plays a crucial role in Eca-109 cell growth. Additionally, the downregulation of KLK10 induced S-phase arrest and promoted cisplatin-induced apoptosis. The resutls of the present study suggested that KLK10 is a promising novel marker for the diagnostic and therapeutic target of esophageal cancer.

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Section: Discussionmentioning

confidence: 99%

Upregulated KLK10 inhibits esophageal cancer proliferation and enhances cisplatin sensitivity in vitro

Fan

et al. 2015

Oncology Reports

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“…Since pro-tumorigenic Rab11a-exosomes are secreted under nutrient stress conditions in cancer cell lines (Fan et al, 2019) , our data could be relevant to the study of tumour adaptation mechanisms. Some accessory ESCRT-IIIs have already been associated with human cancer: Ist1 overexpression (OLC1 in human also known as KIAA0174) has been observed in lung, breast and colorectal cancer as well as oesophageal squamous cell carcinoma (Yuan et al, 2008;Ou-Yang et al, 2014;Liu et al, 2014;Li et al, 2014) , and Chmp1A levels are reported to be increased in renal cell and pancreatic carcinomas (Li et al, 2008;Mochida et al, 2012, p. 1). It may be possible to selectively inhibit Rab11a-exosome biogenesis by interfering with accessory ESCRT-III function and therefore block adaptive responses without preventing the ubiquitin-mediated degradation of growth factor receptors in cancer cells.…”

Section: )mentioning

confidence: 99%

Accessory ESCRT-III proteins selectively regulate Rab11-exosome biogenesis inDrosophilasecondary cells

Marie

Fan

Mendes

et al. 2020

Preprint

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Exosomes are secreted nanovesicles with potent signalling activity that are initially formed as intraluminal vesicles (ILVs) in multivesicular endosomes, which subsequently fuse with the plasma membrane. These ILVs are made in both late endosomes and recycling endosomes, the latter marked by the small GTPase Rab11 and generating exosomes with different cargos and functions. Core proteins within four Endosomal Sorting Complex Required for Transport (ESCRT) assemblies (0-III) play key sequential roles in late endosomal exosome biogenesis and ILV-mediated destruction of ubiquitinylated cargos through the endolysosomal system. They also control additional cellular processes, such as cytokinesis and other vesicle budding.By contrast, the functions of several accessory ESCRTs are not well defined. Here we assess the ESCRT-dependency of Rab11-exosomes, using RNA knockdown in Drosophila secondary cells (SCs) of the male accessory gland, which have unusually enlarged Rab11-positive compartments. Unexpectedly, not only are core proteins in all four ESCRT complexes required for Rab11-exosome formation, but also accessory ESCRT-III proteins, CHMP1, CHMP5 and IST1. Suppressing expression of these accessory proteins does not affect other aspects of cell morphology, unlike most core ESCRT knockdowns, and does not lead to accumulation of ubiquitinylated cargos. We conclude that accessory ESCRT-III components have a specific and potentially ubiquitin-independent role in Rab11-exosome generation, which might provide a target for blocking the pro-tumorigenic activities of these vesicles in cancer.

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“…Previous studies have demonstrated that OLC1 is an oncogenic protein, as the induced overexpression of OLC1 results in anchorage-independent growth in vitro and malignant transformation in vivo . Additionally, OLC1 has been identified as overexpressed in multiple types of malignant tumor, including in lung cancer and esophageal squamous carcinoma (1,2). Thus, additional experiments were performed to confirm if the cells with mutated OLC1 may exhibit more malignant characteristics.…”

Section: Resultsmentioning

confidence: 99%

“…A stable OLC1-overexpressing cell line KYSE150/GFP-OLC1 and its null control cell line KYSE150/GFP were constructed as previously described (2). H1299 human lung carcinoma cells were purchased from the American Type Culture Collection (Manassas, VA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…It was identified that OLC1 was more highly expressed in squamous cell lung tumors compared with normal bronchial epithelial cells, and that it promoted tumor formation in nude mice. Similarly, it was also demonstrated that OLC1 was up regulated in human esophageal carcinoma and contributed to the proliferation of esophageal cancer cells (2).…”

Section: Introductionmentioning

confidence: 95%

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Regulation of OLC1 protein expression by the anaphase‑promoting complex

et al. 2019

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Overexpressed in lung cancer 1 (OLC1) is a potential oncogene overexpressed in human lung cancer and in other types of malignant tumor. The elevated expression of OLC1 contributes to tumor genesis and progression. However, the mechanisms regulating the expression of OLC1 remain unclear. In the present study, using lung and esophageal cancer cell lines, it was demonstrated that OLC1 was a short-lived, cell cycle-dependent protein regulated through the anaphase-promoting complex/cyclosome (APC/c)-ubiquitin pathway by directly interacting with the APC2 subunit. Through the action of two co activator proteins, cadherin 1 (Cdh1) and cell-division cycle protein 20 (Cdc20), the OLC1 protein was ubiquitinated and degraded. Following treatment with a proteasome inhibitor, OLC1 protein levels were elevated. Inversely, the upregulation of Cdh1 and Cdc20 facilitated OLC1 degradation. By inducing point mutations of the assumed degradation motif of OLC1, it was revealed that an intact destruction (D)-box was necessary. As expected, the D-box-mutated OLC1 exhibited a higher capacity for promoting cell growth and clone formation. Collectively, these findings indicate that the expression of the candidate oncogene OLC1 is cell cycle-dependent and is regulated by an APC/c mediated ubiquitin-proteasome pathway.

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Overexpression of OLC1 Promotes Tumorigenesis of Human Esophageal Squamous Cell Carcinoma

Cited by 8 publications

References 45 publications

Upregulated KLK10 inhibits esophageal cancer proliferation and enhances cisplatin sensitivity in vitro

Upregulated KLK10 inhibits esophageal cancer proliferation and enhances cisplatin sensitivity in vitro

Accessory ESCRT-III proteins selectively regulate Rab11-exosome biogenesis inDrosophilasecondary cells

Regulation of OLC1 protein expression by the anaphase‑promoting complex

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