HER2/HER3 regulates extracellular acidification and cell migration through MTK1 (MEKK4)

Sollome, James; Thavathiru, Elangovan; Camenisch, Todd D.; Vaillancourt, Richard

doi:10.1016/j.cellsig.2013.08.043

Cited by 20 publications

(21 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, OIS1 overexpression exhibited no significant effects on the proliferation of HPV-negative or -positive normal cervical cell lines. The regulation of cell migration by MTK-1 has been demonstrated (20). In the present study, MTK-1 positively regulated the proliferation of HPV-positive cervical squamous cell carcinoma cell lines, but not any other cell lines.…”

Section: Discussionsupporting

confidence: 41%

Long non‑coding RNA‑OIS1 inhibits HPV‑positive, but not HPV‑negative cervical squamous cell carcinoma by upregulating MTK‑1

Zhou

Cui

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

Long non-coding RNA-oncogene-induced senescence 1 (lncRNA-OIS1) is a novel lncRNA that is involved in oncogene-induced senescence, while its functionality in cervical squamous cell carcinoma is unknown. In the present study, 68 human papillomavirus (HPV)-positive and 22 HPV-negative patients with cervical squamous cell carcinoma were recruited. Additionally, 40 healthy females were employed as healthy controls. Tumor tissues and adjacent healthy tissues were collected from all patients with cervical squamous cell carcinoma, and blood samples were obtained. Expression of OIS1 was detected by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of OIS1 for cervical squamous cell carcinoma. HPV-positive and HPV-negative cervical squamous cell carcinoma and normal cervical cell lines were used, and the effects of OIS1 or mitogen-activated protein kinase kinase kinase 4, (MTK-1) expression vector transfection on the proliferation of cell lines and MTK-1 expression were detected by CCK-8 assay and western blotting, respectively. It was established that a reduction in OIS1 expression level in tumor tissues was apparent only in HPV-positive patients. Serum levels of OIS1 were lower in HPV-positive patients compared with that in HPV-negative patients and healthy controls, and no significant differences were observed between HPV-negative patients and healthy controls. Serum levels of OIS1 were significantly associated with tumor size, but not distant tumor metastasis. OIS1 expression level was lower in HPV-positive cancer cell lines compared with that in HPV-negative cancer cell lines, while no significant differences were observed between HPV-positive and HPV-negative normal cell lines. OIS1 overexpression inhibited and MTK-1 overexpression promoted the proliferation of HPV-positive, but not HPV-negative cancer or normal cell lines. OIS1 transfection also decreased the expression of MTK-1 in HPV-positive cancer cell lines, but not in any of the other cell lines. Therefore, it was concluded that OIS1 inhibited HPV-positive, but not HPV-negative cervical squamous cell carcinoma by upregulating MTK-1.

show abstract

Section: Discussionsupporting

confidence: 41%

Long non‑coding RNA‑OIS1 inhibits HPV‑positive, but not HPV‑negative cervical squamous cell carcinoma by upregulating MTK‑1

Zhou

Cui

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…A weak correlation was observed between HER2 and HER3 levels, supporting the potential formation of HER2/HER3 heterodimers in patients with OPSCC. The high levels of heregulin expression in HNSCC compared with other tumor types further support a role for the heregulin/HER2/ HER3 trimeric complex in this disease, which has been linked to cell migration, 43,44 tumor cell survival, and drug resistance. 45 Increasing evidence has supported an inverse relationship between EGFR expression and p16 status in patients with HNSCC.…”

Section: Discussionmentioning

confidence: 76%

Heregulin and HER3 are prognostic biomarkers in oropharyngeal squamous cell carcinoma

Qian

Jiang

Wang

et al. 2015

Cancer

View full text Add to dashboard Cite

BACKGROUND Although heregulin and HER3 are frequently expressed at high levels in head and neck cancer, their prognostic value remains unclear. We explored the prognostic significance of heregulin/HER3 expression in patients with oropharyngeal squamous cell carcinoma (OPSCC), taking into account other HER family members as well as p16 status. METHODS Ninety-six primary tumor specimens from OPSCC patients were retrospectively collected and analyzed for heregulin mRNA by in situ hybridization and for HER3, EGFR, and HER2 by quantitative immunohistochemistry. Heregulin and HER3 mRNA levels were also examined among different tumor types using The Cancer Genome Atlas (TCGA) database. RESULTS High heregulin mRNA (> median) correlated significantly with poor OS (HR: 8.48; 95% CI: 2.17–33.17; P = 0.002) but not DFS (HR: 1.52; 95% CI: 0.64–3.65; P = 0.344), in OPSCC patients. Heregulin mRNA correlated negatively with OS in both p16-positive (P = 0.049) and p16-negative (P = 0.091) OPSCC patients on univariate analysis. High HER3 (> median) also correlated with poor OS (HR: 4.68; 95%CI: 1.47–14.90; P = 0.009) on multivariate analysis. EGFR levels independently correlated with DFS (P = 0.025) and inversely correlate with p16 status (P = 0.012). In addition, TCGA data showed that head and neck squamous cell carcinoma exhibits higher heregulin expression compared to other solid tumor types examined. CONCLUSION: High heregulin mRNA and high HER3 protein levels independently correlate with poor OS in OPSCC. These data support targeting HER3 in heregulin-high OPSCC and warrant further clinical investigation.

show abstract

“…2D). Also more significantly upregulated by HNF4␣8 were PIM1, an oncogenic serine/threonine kinase gene (83), and ERBB3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinase genes (84) (Fig. 4D).…”

Section: Generation and Characterization Of Isoform-specific Hnf4␣-exmentioning

confidence: 99%

Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells

Vuong

Chellappa

Dhahbi

et al. 2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

The nuclear receptor hepatocyte nuclear factor 4␣ (HNF4␣) is tumor suppressive in the liver but amplified in colon cancer, suggesting that it also might be oncogenic. To investigate whether this discrepancy is due to different HNF4␣ isoforms derived from its two promoters (P1 and P2), we generated Tet-On-inducible human colon cancer ( Thus, the HNF4␣ isoforms play distinct roles in colon cancer, which could be due to differential interactions with the Wnt/␤-catenin/TCF4 and AP-1 pathways.

show abstract

HER2/HER3 regulates extracellular acidification and cell migration through MTK1 (MEKK4)

Cited by 20 publications

References 82 publications

Long non‑coding RNA‑OIS1 inhibits HPV‑positive, but not HPV‑negative cervical squamous cell carcinoma by upregulating MTK‑1

Long non‑coding RNA‑OIS1 inhibits HPV‑positive, but not HPV‑negative cervical squamous cell carcinoma by upregulating MTK‑1

Heregulin and HER3 are prognostic biomarkers in oropharyngeal squamous cell carcinoma

Differential Effects of Hepatocyte Nuclear Factor 4α Isoforms on Tumor Growth and T-Cell Factor 4/AP-1 Interactions in Human Colorectal Cancer Cells

Contact Info

Product

Resources

About