Oncogene<i>GAEC1</i>regulates<i>CAPN10</i>expression which predicts survival in esophageal squamous cell carcinoma

Chan, Dessy; Tsoi, Miriam Yuen-Tung; Liu, Christina Di; Chan, Sau-Hing; Law, Simon; Chan, Keith; Chan, Yuen-Piu; Gopalan, Vinod; Lam, Alfred King‐Yin; Tang, Johnny

doi:10.3748/wjg.v19.i18.2772

Cited by 25 publications

(18 citation statements)

References 38 publications

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“…Unexpectedly, sample 40 which had no mutation and had a TT allele at rs803097 (results not shown) also showed overexpression of GAEC1 (Figure 8a & 8b). These findings further strengthens the oncogenic and growth promoting properties of GAEC1 (Law et al, 2007;Wahab et al, 2017;Chan et al, 2013;Gopalan et al, 2010;Gopalan et al, 2013).…”

Section: Discussionsupporting

confidence: 71%

“…On the other hand, knockdown of GAEC1 fully suppressed xenograft tumour growth in mice (Wahab et al, 2017). In vitro analysis also showed that knockdown of GAEC1 inhibited cell proliferation, reduced cell migration capacity, decreased clonogenic potentiality and induced apoptosis in both oesophageal squamous cell carcinoma (Chan et al, 2013) and colon cancer cells (Wahab et al, 2017). In addition, knockdown of SW480, SW48 and HCT 116 cells were cultured in RPMI (Roswell Park Memorial Institute) 1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin and incubated in a 37°C incubator supplemented with 5% CO2.…”

Section: Introductionmentioning

confidence: 94%

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GAEC1 mutations and copy number aberration is associated with biological aggressiveness of colorectal cancer

Lee

Gopalan

Islam

et al. 2018

European Journal of Cell Biology

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GAEC1 (gene amplified in oesophageal cancer 1) is a transforming oncogene with tumorigenic potential observed in both oesophageal squamous cell carcinoma and colorectal cancer. Nonetheless, there has been a lack of study done on this gene to understand how this gene exert its oncogenic properties in cancer. This study aims to identify novel mutation sites in GAEC1. To do so, seventy-nine matched colorectal cancers were tested for GAEC1 mutation via Sanger sequencing. The mutations noted were investigated for the correlations with the clinicopathological parameters of the patients with the cancer. Additionally, GAEC1 copy number aberration (CNA), mRNA and protein expression were determined with the use of droplet digital (dd) polymerase chain reaction (PCR), real-time PCR and Western blot (confirmed with immunofluorescence analysis). GAEC1 mutation was noted in 8.8% (n = 7/79) of the cancer tissues including one missense mutation, four loss of heterozygosity (LOH) and two substitutions. These mutations were significantly associated with cancer perforation (p = 0.021). GAEC1 mutation is frequently associated with increased GAEC1 protein expression. Nevertheless, GAEC1 mRNA and protein are only weakly associated. Taken together, GAEC1 mutation affects GAEC1 expression and is associated with poorer clinical outcomes. This further strengthens the role of GAEC1 as an oncogene.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 94%

GAEC1 mutations and copy number aberration is associated with biological aggressiveness of colorectal cancer

Lee

Gopalan

Islam

et al. 2018

European Journal of Cell Biology

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“…Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Asian countries and one of the most common malignancies worldwide [1,2]. This cancer encompasses complex molecular pathology because of its multifaceted genetic and epigenetic alterations [3][4][5][6][7]. These alterations include aberrant expression of key regulatory genes, thereby providing a selective force for cancer development.…”

Section: Introductionmentioning

confidence: 99%

FAM134B promotes esophageal squamous cell carcinoma in vitro and its correlations with clinicopathologic features

et al. 2019

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Family with sequence similarity 134, member B (FAM134B) is an autophagy regulator of endoplasmic reticulum first discovered to be involved in the pathogenesis of esophageal squamous cell carcinoma (ESCC). The present study examined the functional behavior of FAM134B in cancer cells and the association of FAM134B expression with clinicopathologic factors in patients with ESCC. Expression at both the mRNA and protein levels was investigated using real-time polymerase chain reaction and immunohistochemistry. The results were correlated with the clinical and pathological features of the patients. In addition, in vitro functional assays were used to investigate the roles of FAM134B in ESCC cells in response to gene silencing with shRNA lentiviral particles. Overexpression of FAM134B mRNA and protein was present in 31.2% (n = 29/93) and 36.6% (n = 41/112), respectively, in tumors, whereas downregulation occurred in 39.8% (n = 37/93) and 63.4% (n = 71/112), respectively. Expression of FAM134B protein in ESCC correlated with histologic grade (P = .002) and pathologic stage (P = .012). In vitro suppression of FAM134B in ESCC induced significant reductions of cell proliferation and colony formation (P < .05). In addition, suppression of FAM134B caused reduction of wound healing, migration, and invasion capacities of ESCC. To conclude, FAM134B could play crucial roles in the initiation and progression of ESCC, and FAM134B protein expression has potential predictive value. Therefore, development of strategies targeting FAM134B could have therapeutic value in the management of patients with ESCC.

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“…Cell migration is dependent on Rab7a expression, and Rab7a provides a directional effect on vimentin (Margiotta et al, 2017). The high expression of CAPN10 suggests a good prognosis for esophageal squamous cell carcinoma (Chan et al, 2013), however, the high expression of CAPN10 in this study suggests a poor prognosis for HCC. These findings indicate that up-regulated ATGs affect multi-system tumor progression and prognosis, and have different mechanisms of action in different tumors.…”

Section: Discussionmentioning

confidence: 52%

Autophagy-related genes prognosis signature as potential predictive markers for immunotherapy in hepatocellular carcinoma

Mao¹,

Zhang²,

Zhao³

et al. 2020

PeerJ

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Autophagy-related genes (ATGs) depress tumorigenesis. However, in tumor tissue, it promotes tumor progression. Here, we demonstrated that 63 ATGs were differentially expressed in normal tissues and tumor tissues of hepatocellular carcinoma (HCC), and seven prognostic-related genes were chosen to establish prognostic risk signatures. It is not just an independent prognostic factor for HCC, but also closely related to the degree of malignancy of HCC. Further, the hallmarks of PI3K–AKT–mTOR signaling was significantly enriched in the high-risk group. Moreover, AKT–pS473 and mTOR–pS2448 expression was down-regulated and correlated with patient prognosis in high-risk group. Finally, we demonstrate that the prognosis signature of ATGs is closely related to immune cell infiltration and PD-L1 expression. In conclusion, ATGs are a crucial factor in the malignant progression of HCC and will be a new prognostic marker for diagnosis and treatment. ATGs prognostic signatures are potentially useful for predicting PD-L1 therapeutic effects.

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OncogeneGAEC1regulatesCAPN10expression which predicts survival in esophageal squamous cell carcinoma

Abstract: GAEC1 regulates the expression of CAPN10 and TNRC6C downstream. Calpain 10 expression is a potential prognostic marker in patients with esophageal squamous cell carcinoma.

Cited by 25 publications

References 38 publications

GAEC1 mutations and copy number aberration is associated with biological aggressiveness of colorectal cancer

GAEC1 mutations and copy number aberration is associated with biological aggressiveness of colorectal cancer

FAM134B promotes esophageal squamous cell carcinoma in vitro and its correlations with clinicopathologic features

Autophagy-related genes prognosis signature as potential predictive markers for immunotherapy in hepatocellular carcinoma

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