Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma

Panaccione, Alex; Zhang, Yi; Mi, Yanfang; Mitani, Yoshitsugu; Guo, Yan; Prasad, Manju L.; El‐Naggar, Adel K.; Yarbrough, Wendell G.; Ivanov, Sergey V.

doi:10.1016/j.oraloncology.2016.12.011

Cited by 19 publications

(11 citation statements)

References 60 publications

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“…Three salivary epithelial-derived carcinoma cell lines, A253, RET981, 23,25 and MAC 26 were used. A253 is ATCC cell line (American Type Culture Collection, Manassas, VA) developed from salivary epidermoid carcinoma (squamous-like) and may represent primary mucoepidermoid carcinoma cells.…”

Section: In Vitro Cell Line Studiesmentioning

confidence: 99%

Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy

Saintigny

Mitani

Pytynia

et al. 2018

Cancer

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BACKGROUND Patients with advanced primary and recurrent salivary duct carcinoma (SDC), a rare and lethal malignancy, have limited therapeutic options. Novel small molecule agents aimed at targeting critical signaling associated with SDC tumorigenesis may lead to new therapeutic options in patients with these tumors. The HER2/PI3K axis, an important oncogenic pathway, has been targeted for therapy in several solid tumors. Currently, little is known on the role and clinical implications of alterations of the HER2/PI3K pathway in SDC. METHODS We investigated the clinicopathologic, genetic alterations and expression of key members of the HER2/PI3K pathway in 43 primary tumors and conducted in vitro functional and targeted drug response on cell lines derived from salivary epithelial carcinomas. RESULTS In primary tumors, loss of PTEN expression was found in 51% (22/43), overexpression of HER2 was observed in 28% (12/43) and PIK3CA mutations were identified in 28% (12/43) of tumors. Phospho-AKT (p-AKT) was highly expressed in most tumors. The majority of tumors (70%) displayed mutually exclusive alterations of PI3K members, while eight (19%) tumors had two or more concurrent abnormalities. In vitro studies demonstrated direct association between PTEN loss and PI3K pathway activation and evidence of response to combined PI3Kα and β and/or pan-PI3K inhibitors. CONCLUSIONS Our study reveals frequent PTEN loss and mutually exclusive alterations of key PI3K pathway members in SDCs and demonstrates in vitro evidence for response to pan-PI3K inhibitors. The study provides a framework for biomarker based sub-stratification of SDC patients’ in future targeted therapy.

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Section: In Vitro Cell Line Studiesmentioning

confidence: 99%

Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy

Saintigny

Mitani

Pytynia

et al. 2018

Cancer

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“…Multiple molecular abnormalities may contribute to aggressive behavior, possibly via the epigenetic regulation of CSCs (32). The present study demonstrated that the expression levels of Ezh2, SUZ12 and EED, which are components of the polycomb-repressive complex 2 (PRC2), were decreased by ZNF750 overexpression.…”

Section: Discussionmentioning

confidence: 52%

Zinc‑finger protein 750 mitigates malignant biological behavior of oral CSC‑like cells enriched from parental CAL‑27 cells

Yang

et al. 2021

Oncol Lett

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Oral squamous cell carcinoma (OSCC) is the most commonly occurring oral malignancy. Cancer stem cells (CSCs) are known to be responsible for cancer recurrence and metastasis. Zinc-finger protein 750 (ZNF750) has been reported to inhibit OSCC cell proliferation and invasion. The present study aimed to elucidate the role of ZNF750 in the inhibition of the renewal ability of CSCs derived from the OSCC cell line, CAL-27. The effects of ZNF750 on CSC-like properties were examined using aldehyde dehydrogenase (ALDH), tumor sphere formation and colony formation assays. Reverse transcription-quantitative PCR and western blotting were performed to detect the expression levels of octamer-binding transcription factor 4, sex-determining region Y-box 2, the enhancer of zeste homolog 2 (Ezh2), embryonic ectoderm development (EED) and SUZ12 polycomb repressive complex 2 subunit (SUZ12), and for the identification of genes associated with metastasis. ZNF750 effectively attenuated CSC-like cell self-renewal abilities; ZNF750 decreased the ALDH-positive cell population, tumor sphere and colony formation abilities, cell viability and stemness factors. Furthermore, the expression levels of Ezh2, EED and SUZ12 were decreased by ZNF750. ZNF750 inhibited MMP1, 3, 9 and 13 expression levels, and decreased the cell invasion and migratory abilities. Moreover, the expression of tissue inhibitors of matrix metalloproteinases-1 was increased by ZNF750. However, opposite effects were observed following the knockdown of the ZNF750 gene. Overall, the present study demonstrated that ZNF750 has the potential to inhibit the renewal of CSC-like cells enriched from parental CAL-27 cells.

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“…This system allows the direct study of the human tumour, which as such maintains its original heterogeneity and molecular identity in the implant. This is very useful for the evaluation of the response to therapies, proving to have, therefore, a high value for the drug screenings in the clinic [18,39]. Schuh et al have recently published a systematic review on the translational applicability of this model [19].…”

Section: Pdx Animal Modelsmentioning

confidence: 99%

Preclinical models in Head and Neck Squamous Cell Carcinoma

Chaves¹,

Garrido²,

Oliver³

et al. 2022

Preprint

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Head and neck cancer is the sixth most frequent cancer type. Drug resistance and toxicity are common challenges of the existing therapies, making the development of reliable preclinical models essential for the study of the involved molecular mechanisms as well as for eventual intervention approaches that improve the clinical outcome. Preclinical models of head and neck squamous cell carcinoma have been traditionally based in cell lines and murine models. In this review, we will go over the most frequently used preclinical models, from immortalized-cell and primary tumour cultures in monolayer or 3D, to the currently available animal models. We will scrutinize their efficiency in mimicking the molecular and cellular complexity of head and neck squamous cell carcinoma. Finally, the challenges and opportunities of other envisaged putative approaches, as well as the potential of the preclinical models to further develop customized therapies will be discussed.

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Chromosomal abnormalities and molecular landscape of metastasizing mucinous salivary adenocarcinoma

Cited by 19 publications

References 60 publications

Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy

Frequent PTEN loss and differential HER2/PI3K signaling pathway alterations in salivary duct carcinoma: Implications for targeted therapy

Zinc‑finger protein 750 mitigates malignant biological behavior of oral CSC‑like cells enriched from parental CAL‑27 cells

Preclinical models in Head and Neck Squamous Cell Carcinoma

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