2021
DOI: 10.1038/s41419-021-04211-8
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Transmembrane protein 97 exhibits oncogenic properties via enhancing LRP6-mediated Wnt signaling in breast cancer

Abstract: Upregulation of transmembrane protein 97 (TMEM97) has been associated with progression and poor outcome in multiple human cancers, including breast cancer. Recent studies suggest that TMEM97 may be involved in the activation of the Wnt/β-catenin pathway. However, the molecular mechanism of TMEM97 action on Wnt/β-catenin signaling is completely unclear. In the current study, TMEM97 was identified as an LRP6-interacting protein. TMEM97 could interact with LRP6 intracellular domain and enhance LRP6-mediated Wnt s… Show more

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Cited by 19 publications
(10 citation statements)
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“…On the other hand, discrepant results from S2R pharmacological modulation and TMEM97 ablation have been recently observed by other investigators. For example, whereas anti-cancer properties have been traditionally attributed to putative S2R agonists [ 43 , 49 , 50 ], tumor growth was suppressed by TMEM97/S2R knockout in a breast cancer xenograft model [ 51 ]. Furthermore, a recent report from the Mach group suggested that TMEM97 does not mediate S2R ligand-induced cytotoxicity of HeLa cells [ 52 ].…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, discrepant results from S2R pharmacological modulation and TMEM97 ablation have been recently observed by other investigators. For example, whereas anti-cancer properties have been traditionally attributed to putative S2R agonists [ 43 , 49 , 50 ], tumor growth was suppressed by TMEM97/S2R knockout in a breast cancer xenograft model [ 51 ]. Furthermore, a recent report from the Mach group suggested that TMEM97 does not mediate S2R ligand-induced cytotoxicity of HeLa cells [ 52 ].…”
Section: Discussionmentioning
confidence: 99%
“…During activation of this pathway, WNT binding to Frizzled receptors and LRP5/6 coreceptors results in the recruitment of the cytosolic effector Dishevelled (DVL), which prevents degradation of β-catenin. 38 This leads to β-catenin accumulating steadily in cells, which is subsequently transferred to the nucleus to kick-start downstream signaling activation. CCND1 was a confirmed target gene of WNT/β- catenin, and its upregulation could promote cell proliferation by enhancing cell cycle progression.…”
Section: Journal Of Agricultural and Food Chemistrymentioning
confidence: 99%
“…6,7,16−20 The σ 2 receptor/TMEM97, progesterone receptor membrane component 1 (PGRMC1), and low-density lipoprotein receptor (LDLR) were reported to form a trimeric complex to accelerate the internalization of LDL in proliferating versus quiescent tumor cells. 21 In addition, the σ 2 receptor/TMEM97 has also been regarded as a potential therapeutic target in human glioma, 22 squamous cell carcinoma of the lung (SQCLC), 23 gastric cancer, 24 colorectal cancer (CRC), 25 nasopharyngeal carcinoma, 26 hepatocellular carcinoma (HCC), 27 breast cancer, 28 and pancreatic cancer. 29 Therefore, noninvasive positron emission tomography (PET) imaging with suitable radioligand of high affinity, selectivity, and specificity for the σ 2 receptor/TMEM97 can visualize the proliferative status of tumors and help monitor the mechanism and treatment effects of new therapeutic approaches.…”
Section: ■ Introductionmentioning
confidence: 99%
“…The σ 2 receptor/TMEM97 has attracted increasing interests due to its involvements in the pathophysiology of various cancers and brain disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, neuropathic pain, drug addiction, and depression. , CT1812, an antagonist of the σ 2 receptor, has proven to be effective for the treatment of AD in clinical trials. ,, In the past decades, the σ 2 receptor/TMEM97 has been proposed as a biomarker for the proliferative status of solid tumors in light of its approximately 10-fold higher expression in proliferating than quiescent tumors. ,,− The σ 2 receptor/TMEM97, progesterone receptor membrane component 1 (PGRMC1), and low-density lipoprotein receptor (LDLR) were reported to form a trimeric complex to accelerate the internalization of LDL in proliferating versus quiescent tumor cells . In addition, the σ 2 receptor/TMEM97 has also been regarded as a potential therapeutic target in human glioma, squamous cell carcinoma of the lung (SQCLC), gastric cancer, colorectal cancer (CRC), nasopharyngeal carcinoma, hepatocellular carcinoma (HCC), breast cancer, and pancreatic cancer . Therefore, noninvasive positron emission tomography (PET) imaging with suitable radioligand of high affinity, selectivity, and specificity for the σ 2 receptor/TMEM97 can visualize the proliferative status of tumors and help monitor the mechanism and treatment effects of new therapeutic approaches.…”
Section: Introductionmentioning
confidence: 99%