STC2 is upregulated in hepatocellular carcinoma and promotes cell proliferation and migration in vitro

Wang, Hai-Xiao; Wu, Kuang Jie; Sun, Yuan; Li, Yan Dong; Wu, Ming; Qiao, Qian; Wei, Yuan; Han, Ze‐Guang; Cai, Bing

doi:10.5483/bmbrep.2012.45.11.086

Cited by 58 publications

(48 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STC2 expression is stimulated by hypoxia and/or unfolded protein responses in human cancers . Recent in vitro evidence support the notion that STC2 is associated with aggressive cancer phenotypes in ovarian, breast and hepatocellular carcinoma . Furthermore, it has been reported that human STC2 is a HIF‐1 target gene and the upregulation of STC2 expression stimulated growth of human ovarian and breast cancer cells (for example, SKOV3 and MCF7) under hypoxic conditions .…”

Section: Discussionmentioning

confidence: 88%

Anti-VEGF antibody therapy induces tumor hypoxia and stanniocalcin 2 expression and potentiates growth of human colon cancer xenografts

et al. 2014

View full text Add to dashboard Cite

Tumor angiogenesis plays a critical role in colorectal cancer progression. Recent randomized clinical trials have revealed the additive effect of bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF)‐A, to conventional chemotherapy in the improved survival of patients with metastatic colorectal cancer. However, a number of preclinical reports indicate the development of resistance to anti‐angiogenic therapy. In this study, we addressed the effects of anti‐VEGF antibodies on the growth and malignant behavior of colorectal cancer cells. TK‐4, a solid tumor strain derived from a colon cancer patient, was subcutaneously or orthotopically implanted into nude mice. Short‐term administration of anti‐VEGF antibodies inhibited the growth of cecal tumors at day 14 by suppressing mitosis, but prolonged treatment resulted in the recovery of cellular proliferation and suppression of apoptosis at day 35. Intratumoral hypoxia induced by anti‐VEGF antibody treatment resulted in activation of hypoxia inducible factor‐1α protein and an increased number of aldehyde dehydrogenase 1‐positive tumor cells. In microarray analysis, stanniocalcin 2 (STC2) was the most highly upregulated gene in anti‐VEGF antibody‐treated tumors. In vitro analyses showed that the growth and migration of SW480 colon cancer cells under hypoxic conditions were significantly inhibited by knockdown of STC2. In vivo serial transplantation of TK‐4 revealed that long‐term administration of anti‐VEGF antibodies increased the tumorigenicity of colon cancers and accelerated tumor growth when transplanted into secondary recipient mice. Our data provide a potential molecular explanation for the limited clinical effectiveness of anti‐VEGF antibodies.

show abstract

Section: Discussionmentioning

confidence: 88%

Anti-VEGF antibody therapy induces tumor hypoxia and stanniocalcin 2 expression and potentiates growth of human colon cancer xenografts

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Several reports suggest elevated expression of STC2 in human hepatocellular carcinoma, neuroblastoma, breast cancer, colorectal cancer, renal cell carcinoma, esophageal squamous cell cancer, and prostate cancer (41,(64)(65)(66)(67)(68)(69). Additionally, expression of STC2 was correlated with tumor invasion, metastasis and size in gastric cancers and hepatocellular carcinoma (70). In gastric cancer patients, STC2 expression in circulating tumor cells as well as serum STC2 levels were positively correlated with pathological diagnosis and prognosis (71,72).…”

Section: Tumor Biologymentioning

confidence: 98%

New Insights Into Physiological and Pathophysiological Functions of Stanniocalcin 2

Joshi

2020

Front. Endocrinol.

View full text Add to dashboard Cite

Stanniocalcin, a glycosylated peptide hormone, first discovered in a bony fish has originally been shown to play critical role in calcium and phosphate homeostasis. Two paralogs of stanniocalcin (STC1 and STC2) identified in mammals are widely expressed in variety of tissues. This review provides historical perspective on the discovery of fish and mammalian stanniocalcin, describes molecular regulation of STC2 gene, catalogs distribution as well as expression of STC2 in tissues, and provides key structural information known till date regarding mammalian STC2. Additionally, this mini review summarizes pivotal functions of STC2 in calcium and phosphate regulation, cytoprotection, cell development, and angiogenesis. Finally, STC2's role as a novel marker for human cancers has also been outlined. Reviewing these studies will provide an opportunity to understand STC2's structure, biological functions as well as key molecular pathways involving STC2, which will help us design innovative therapeutic interventions using this novel hormone.

show abstract

“…b ). STC2 and AXL were known to induce EMT . We investigated whether STC2 increased cell migration and induced mesenchymal‐like genotype in lung cancer.…”

Section: Resultsmentioning

confidence: 99%

Acquired resistance to EGFR tyrosine kinase inhibitors is mediated by the reactivation of STC2/JUN/AXL signaling in lung cancer

Liu

Tsai

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

Constitutive activation of the epidermal growth factor receptor (EGFR) signaling pathway is implicated in the initiation and progression of lung cancer. EGFR tyrosine kinase inhibitor (TKI)-targeted therapy has become the standard treatment for nonsmall cell lung cancer (NSCLC) patients. However, acquired resistance to these agents remains a major obstacle for managing NSCLC. Here, we investigated a novel strategy to overcome EGFR TKI resistance by targeting the stanniocalcin 2 (STC2)-JUN-AXL pathway. We revealed that STC2 was expressed at significantly higher levels in EGFR TKI-resistant cells. Further, clinical analysis showed that STC2 expression was increased after the development of EGFR TKI resistance and that higher levels were correlated with shorter progression-free survival in EGFR TKI-treated lung cancer patients. Moreover, STC2 overexpression in EGFR TKI-sensitive cells resulted in EGFR TKI resistance. Conversely, genetic silencing of STC2 rendered EGFR TKI-resistant cells more sensitive to EGFR TKIs. Mechanically, STC2 enhanced AXL promoter activity by increasing the phosphorylation of c-Jun, which is an indispensable transcription factor that transactivates AXL. STC2 promoted activation of the JUN-AXL-extracellular signal-regulated kinase (ERK) signaling axis in lung cancer cells. Pharmacological or genetic inhibition of AXL-ERK activity inhibited STC2-mediated EGFR TKI resistance. We also demonstrated that PE2988 cells, a C797Sindependent osimertinib-resistant primary cancer cell line from a lung cancer patient, responded to combined AXL inhibitor and osimertinib treatment. In conclusion, our research indicates that STC2 overexpression is important for acquired resistance to EGFR TKIs and that STC2-JUN-AXL-ERK signaling might be a potential therapeutic target to overcome resistance to EGFR TKIs.

show abstract

STC2 is upregulated in hepatocellular carcinoma and promotes cell proliferation and migration in vitro

Cited by 58 publications

References 27 publications

Anti-VEGF antibody therapy induces tumor hypoxia and stanniocalcin 2 expression and potentiates growth of human colon cancer xenografts

Anti-VEGF antibody therapy induces tumor hypoxia and stanniocalcin 2 expression and potentiates growth of human colon cancer xenografts

New Insights Into Physiological and Pathophysiological Functions of Stanniocalcin 2

Acquired resistance to EGFR tyrosine kinase inhibitors is mediated by the reactivation of STC2/JUN/AXL signaling in lung cancer

Contact Info

Product

Resources

About