Solute Carrier Family 39 Member 6 Gene Promotes Aggressiveness of Esophageal Carcinoma Cells by Increasing Intracellular Levels of Zinc, Activating Phosphatidylinositol 3-Kinase Signaling, and Up-regulating Genes That Regulate Metastasis

Cheng, Xinxin; Wei, Lixuan; Huang, Xudong; Zheng, Jian; Shao, Mingming; Feng, Ting; Li, Jun; Han, Yaling; Tan, Wenle; Tan, Wen; Lin, Dong; Wu, Chen

doi:10.1053/j.gastro.2017.02.006

Cited by 46 publications

(37 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The enzyme is also considered to be involved in wound repair, atherosclerosis progression and tumorigenesis [31]. In another study, the expressions of SLUG, MMP1, MMP3, and MYC were found to be correlated, suggesting that SLUG may play a role as a transcription factor for MMP1 and MMP3 [32]. Our gene microarray results showed that MMP1 and MMP3 were signi cantly upregulated in SLUG overexpressing cells, which was further con rmed by quantitative PCR and western blot.…”

Section: Discussionsupporting

confidence: 69%

SLUG is Enhanced by Chemotherapeutics and Functions to Promote Invasion and Metastasis by Directly Targeting MMP3 in Cervical Cancer

Jiang¹,

Zhang²,

Huang³

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundNeoadjuvant chemotherapy(NACT) is a widely used strategy in the treatment of locally advanced cancers. NACT followed by radical surgery for patients in FIGO stages IB2-IIB has proven to reduce tumor volume and numbers. Under certain conditions, however, NACT followed by radical surgery has not been found to improve overall survival, but rather to accelerate cancer growth and metastasis in current studies.MethodsIn this study, 35 paired pre/post-NACT cervical cancer tissues and 167 cervical cancer samples were examined by immunohistochemical analysis to investigate the role of SLUG in invasion and metastasis. Functional assays and a CHIP assay were performed to determine SLUG’s downstream genes and pathways. A lymph node metastatic mouse model was used to study the effects of SLUG- and MMP3-silencing on the malignant behavior of the cervical cancer cells. ResultsSLUG expression was potentially increased in cervical cancer tissues after neoadjuvant chemotherapy, which in turn positively correlated with pelvic lymph node metastasis. The expression of SLUG following neoadjuvant chemotherapy was identified as a poor survival indicator. SLUG overexpression promoted metastasis in cervical cancer in both in vitro and in vivo models, whereas SLUG silencing had the opposite effect. Mechanically, SLUG is not a prerequisite for EMT activation in cervical cancer models, but contributes to the invasiveness and metastasis of cervical cancer cells by directly tethering to the recognition sequence GCCAGGTGC in the MMP3 promoter region. ConclusionOur results provide mechanistic insight into the potential pro-cancer effect of neoadjuvant chemotherapy, and demonstrates that the SLUG-MMP3 axis could serve as a target for improving the efficacy of chemotherapy.

show abstract

Section: Discussionsupporting

confidence: 69%

SLUG is Enhanced by Chemotherapeutics and Functions to Promote Invasion and Metastasis by Directly Targeting MMP3 in Cervical Cancer

Jiang¹,

Zhang²,

Huang³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…And slug, together with MMP2, MMP9 and c-Myc, have been well characterized as downstream targets of AKT and ERK. [23][24][25][26] Ewald et al said that COL11A1 may promote bladder cancer invasiveness through PI3K/Akt and Ras/ERK signaling pathway. 27 Wu et al highlighted the magnitude of COL11A1 in chemoresistance of ovarian cancer patients through increasing p-AKT expression; comparing to chemo-naive cells, chemoresistant cells exhibited stronger intensity and higher proportion of COL11A1 staining among positive cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic collagen XIαI as a prognostic biomarker in esophageal squamous cell carcinoma

Zhang

Yang

et al. 2018

Cancer Biology & Therapy

View full text Add to dashboard Cite

Stromal/cytoplasmic collagen XIαI (COL11A1) has been highlighted in the process of neoplastic transformation, including epithelial mesenchymal transition (EMT), metastasis and invasiveness. In this study, we aim to illuminate the clinical significance and biological role of COL11A1 in esophageal squamous cell carcinoma (ESCC). Herein, we investigated COL11A1 expression in 16 pairs of ESCC and adjacent normal tissues by RT-PCR and western blotting analysis. Correlations of COL11A1 expression with clinicopathologic parameters and survival status were then determined by immunohistochemistry in 116 ESCC and 50 normal specimens. Furthermore, bioinformatics was used for mechanisms exploration. And in vitro knockdown experiments were also performed. We found that COL11A1 expression was significantly higher in ESCC than in paired normal tissues at both mRNA and protein level. Immunohistochemistry showed that COL11A1 was predominantly localized to the cytoplasm rather than tumor stroma, patients with high COL11A1 expression had a poorer overall survival (OS) rate than those with low COL11A1 expression. Besides, increased COL11A1 expression was dramatically correlated with advanced clinical stage, invasion depth and lymph node metastases and served as an independent prognostic marker for ESCC. Likewise, COL11A1 dependent nomogram predicted a more precise survival outcome than traditional staging system. Moreover, COL11A1 silencing resulted in impaired cell proliferation and EMT, and subdued EMT inhibited cells aggressiveness. These biological processes (BPs) might be modulated by COL11A1 via the intracellular AKT/ERK/c-Myc cascades.

show abstract

“…For example, Xu et al found that amplification of SLC12A5 plays a strong tumorigenic role and is associated with poor prognosis of patients with colorectal cancer . SLC39A6 promotes aggressiveness of esophageal squamous carcinoma cells by increasing intracellular levels of zinc and activates phosphatidylinositol 3‐kinase (PI3K) pathway . SLC35, a group of nucleotide sugar transporters, currently comprises at least 31 homologous molecular species from SLC35A to SLC35G.…”

Section: Introductionmentioning

confidence: 99%

“…6 SLC39A6 promotes aggressiveness of esophageal squamous carcinoma cells by increasing intracellular levels of zinc and activates phosphatidylinositol 3-kinase (PI3K) pathway. 7 SLC35, a group of nucleotide sugar transporters, currently comprises at least 31 homologous molecular species from SLC35A to SLC35G. SLC35A2 functions as a UDP-galactose transporter, whose substrate is required for galactosylation.…”

Section: Introductionmentioning

confidence: 99%

Solute carrier family 35 member F2 is indispensable for papillary thyroid carcinoma progression through activation of transforming growth factor‐β type I receptor/apoptosis signal‐regulating kinase 1/mitogen‐activated protein kinase signaling axis

Jin

Zhou

et al. 2018

Cancer Science

View full text Add to dashboard Cite

Solute carrier family members control essential physiological functions and are tightly linked to human diseases. Solute carrier family 35 member F2 (SLC35F2) is aberrantly activated in several malignancies. However, the biological function and molecular mechanism of SLC35F2 in papillary thyroid carcinoma (PTC) are yet to be fully explored. Here, we showed that SLC35F2 was prominently upregulated in PTC tissues at both protein and mRNA expression level compared with matched adjacent normal tissues. Besides, the high expression of SLC35F2 was significantly associated with lymph node metastasis in patients with PTC. CRISPR/Cas9‐mediated knockout of SLC35F2 attenuated the tumorigenic properties of PTC, including cell proliferation, migration and invasion and induced G1 phase arrest. In contrast, ectopic expression of SLC35F2 brought about aggressive malignant phenotypes of PTC cells. Moreover, SLC35F2 expedited the proliferation and migration of PTC cells by targeting transforming growth factor‐β type I receptor (TGFBR1) and phosphorylation of apoptosis signal‐regulating kinase 1 (p‐ASK‐1), thereby activating the mitogen‐activated protein kinase signaling pathway. The malignant behaviors induced by overexpression of SLC35F2 could be abrogated by silencing of TGFBR1 using a specific inhibitor. We conducted the first study on SLC35F2 in thyroid cancer with the aim of elucidating the functional significance and molecular mechanism of SLC35F2. Our findings suggest that SLC35F2 exerts its oncogenic effect on PTC progression through the mitogen‐activated protein kinase pathway, with dependence on activation of TGFBR‐1 and apoptosis signal‐regulating kinase 1.

show abstract

Solute Carrier Family 39 Member 6 Gene Promotes Aggressiveness of Esophageal Carcinoma Cells by Increasing Intracellular Levels of Zinc, Activating Phosphatidylinositol 3-Kinase Signaling, and Up-regulating Genes That Regulate Metastasis

Cited by 46 publications

References 38 publications

SLUG is Enhanced by Chemotherapeutics and Functions to Promote Invasion and Metastasis by Directly Targeting MMP3 in Cervical Cancer

SLUG is Enhanced by Chemotherapeutics and Functions to Promote Invasion and Metastasis by Directly Targeting MMP3 in Cervical Cancer

Cytoplasmic collagen XIαI as a prognostic biomarker in esophageal squamous cell carcinoma

Solute carrier family 35 member F2 is indispensable for papillary thyroid carcinoma progression through activation of transforming growth factor‐β type I receptor/apoptosis signal‐regulating kinase 1/mitogen‐activated protein kinase signaling axis

Contact Info

Product

Resources

About