Overexpression of Malic Enzyme 2 Indicates Pathological and Clinical Significance in Oral Squamous Cell Carcinoma

Zhou, Junjie; Xiao, Yao; Li, Hao; Wu, Congcong; Chen, De-Run; Chen, Lei; Deng, Wei‐Wei; Zhang, Wenfeng; Sun, Zhi‐Jun

doi:10.7150/ijms.43832

Cited by 3 publications

(3 citation statements)

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“…Studies have shown that in HNCs, ALDH1 is mainly regulated by retinoic acid compounds and other oncogenic pathways such as MUC1-C/ERK and WNT/β-catenin ( 191 ), but also by the AKT signaling pathway ( 192 , 193 ). ALDH1A1 increases TUBB3 expression, which down-regulates PTEN and promotes cell proliferation, migration, and invasion ( 194 ).…”

Section: Aldh1 and Various Solid Tumorsmentioning

confidence: 99%

ALDH1: A potential therapeutic target for cancer stem cells in solid tumors

Wei

Chen

et al. 2022

Front. Oncol.

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Solid tumors can be divided into benign solid tumors and solid malignant tumors in the academic community, among which malignant solid tumors are called cancers. Cancer is the second leading cause of death in the world, and the global incidence of cancer is increasing yearly New cancer patients in China are always the first. After the concept of stem cells was introduced in the tumor community, the CSC markers represented by ALDH1 have been widely studied due to their strong CSC cell characteristics and potential to be the driving force of tumor metastasis. In the research results in the past five years, it has been found that ALDH1 is highly expressed in various solid cancers such as breast cancer, lung cancer, colorectal cancer, liver cancer, gastric cancer, cervical cancer, esophageal cancer, ovarian cancer, head,and neck cancer. ALDH1 can activate and transform various pathways (such as the USP28/MYC signaling pathway, ALDH1A1/HIF-1α/VEGF axis, wnt/β-catenin signaling pathway), as well as change the intracellular pH value to promote formation and maintenance, resulting in drug resistance in tumors. By targeting and inhibiting ALDH1 in tumor stem cells, it can enhance the sensitivity of drugs and inhibit the proliferation, differentiation, and metastasis of solid tumor stem cells to some extent. This review discusses the relationship and pathway of ALDH1 with various solid tumors. It proposes that ALDH1 may serve as a diagnosis and therapeutic target for CSC, providing new insights and new strategies for reliable tumor treatment.

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Section: Aldh1 and Various Solid Tumorsmentioning

confidence: 99%

ALDH1: A potential therapeutic target for cancer stem cells in solid tumors

Wei

Chen

et al. 2022

Front. Oncol.

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“…ME1 is a potential oncogene product linked to energy metabolism, redox status, and epithelial to mesenchymal transition (EMT) in squamous cell carcinoma (oral, head, and neck), breast cancer, and gastric cancer. − ME2 is overexpressed in human primary oral squamous cell carcinoma tissue and in lung carcinoma tissue for helping tumor cell proliferation and colony formation. , ME2 is also known to promote cell proliferation, invasion, and migration of glioma cells in glioblastoma . ME3, a paralogous isoform of ME2, is localized in mitochondria, and its aberrant expression contributes to the carcinogenesis of pancreatic cancer …”

mentioning

confidence: 99%

“…9−11 ME2 is overexpressed in human primary oral squamous cell carcinoma tissue and in lung carcinoma tissue for helping tumor cell proliferation and colony formation. 12,13 ME2 is also known to promote cell proliferation, invasion, and migration of glioma cells in glioblastoma. 14 ME3, a paralogous isoform of ME2, is localized in mitochondria, and its aberrant expression contributes to the carcinogenesis of pancreatic cancer.…”

mentioning

confidence: 99%

In the Quest for Potent and Selective Malic Enzyme 3 Inhibitors for the Treatment of Pancreatic Ductal Adenocarcinoma

Sheth

Shah

Sengupta

et al. 2022

ACS Med. Chem. Lett.

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The genome of pancreatic ductal adenocarcinoma (PDAC) is associated with frequent deletion of the tumor suppressor gene SMAD family member 4 (SMAD4) with collateral deletion of its chromosomal neighbor malic enzyme 2 (ME2). In SMAD4 –/– /ME2 –/– PDAC cells, ME3 takes over the function of the ME2 enzyme, and hence therapeutic targeting of ME3 is expected to arrest tumor growth. Hitherto no selective small molecule inhibitor of ME3 has been reported in the context of PDAC. Based on the molecular docking studies and structure–activity relationships with the reported ME1 inhibitor, several analogues of 6-piperazin-1-ylpyridin-3-ol amides have been synthesized and screened for their ME inhibition activity. Among them, compound 16b is identified as the most potent and selective ME3 inhibitor with an IC50 of 0.15 μM on ME3, and with 15- and 9-fold selectivity over ME1 and ME2, respectively. In the cell viability assay, compound 16b exhibited an IC50 of 3.5 μM on ME2-null PDAC cells, viz., BxPC-3.

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