Aberrant TRPM4 expression in MLL-rearranged acute myeloid leukemia and its blockade induces cell cycle arrest via AKT/GLI1/Cyclin D1 pathway

Wang, Fujue; Wu, Pengqiang; Gong, Shuaige; Chen, Yingying; Gao, Jie; Wang, Shuoting; Shen, Qianqing; Tao, Hongbing; Fang, Hua; Zhou, Zong-Guang; Zou, Zhongqing; Ma, Tao; Jia, Yongyi

doi:10.1016/j.cellsig.2020.109643

Cited by 13 publications

(14 citation statements)

References 26 publications

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“…In acute myeloid leukemia (AML) patients and AML cell lines, expression of TRPM4 is significantly increased. In addition, the knockdown of TRPM4 inhibited proliferation and cell cycle progression through the AKT/GLI1/Cyclin D1 pathways [124]. For liver cancer, urinary bladder cancer, and DLBCL, to date, only expression studies have been performed.…”

Section: Other Cancersmentioning

confidence: 99%

TRPM4 in Cancer—A New Potential Drug Target

2021

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Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, liver, breast, urinary bladder, cervical, and endometrial cancer. In several types of cancer TRPM4 is overexpressed and contributes to cancer hallmark functions such as increased proliferation and migration and cell cycle shift. Hence, TRPM4 is a potential prognostic cancer marker and a promising anticancer drug target candidate. Currently, the underlying mechanism by which TRPM4 contributes to cancer hallmark functions is under investigation. TRPM4 is a Ca2+-activated monovalent cation channel, and its ion conductivity can decrease intracellular Ca2+ signaling. Furthermore, TRPM4 can interact with different partner proteins. However, the lack of potent and specific TRPM4 inhibitors has delayed the investigations of TRPM4. In this review, we summarize the potential mechanisms of action and discuss new small molecule TRPM4 inhibitors, as well as the TRPM4 antibody, M4P. Additionally, we provide an overview of TRPM4 in human cancer and discuss TRPM4 as a diagnostic marker and anticancer drug target.

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Section: Other Cancersmentioning

confidence: 99%

TRPM4 in Cancer—A New Potential Drug Target

2021

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“…TRPM4 was associated with several types of malignant diseases [39]. Usually overexpression of TRPM4 was reported in several types of malignancies, such as prostate cancer [183,184]; breast, cervical, and endometrial cancer [16,[185][186][187]; diffuse large B cell lymphoma [188,189]; and acute myeloid leukemia [190]. TRPM4 protein overexpression was observed in colorectal cancer [191], but other studies reported either no differences in TRPM4 expression [192] or lower TRPM4 mRNA levels in colorectal cancer compared with normal tissue [193].…”

Section: The Role Of Trpm4 In Cancermentioning

confidence: 99%

“…Out of 189 DLBCL cases, 26% exhibited 10-100% TRPM4-positive tumor cells, and the high TRPM4 expression in activated B cell-like DLBCL subtype was associated with a reduced overall and progression-free survival [188]. TRPM4 expression also increased in those acute myeloid leukemia patients and acute myeloid leukemia cell lines where the MLL gene (a methyltransferase for histone H3 lysine 4) was rearranged [190]. TRPM4 KD by siRNA in MLL-rearranged cell lines inhibited proliferation and cell cycle progression through the AKT/GLI1/Cyclin D1 pathways.…”

Section: The Role Of Trpm4 In Cancermentioning

confidence: 99%

“…TRPM4 KD by siRNA in MLL-rearranged cell lines inhibited proliferation and cell cycle progression through the AKT/GLI1/Cyclin D1 pathways. The transcription factor HOXA9 was found to be responsible for the upregulation of TRPM4 expression by binding to its promoter in MLL rearranged cell lines [190]. The up-regulation of TRPM4, the only surface protein among up-regulated gene products in acute myeloid leukemia cell lines made TRPM4 a potential novel therapeutic target [198].…”

Section: The Role Of Trpm4 In Cancermentioning

confidence: 99%

“…As mentioned above, the role of TRPM4 in cancer is often based on observations where it exhibits a different expression compared with control tissues; sometimes the correlation between the amount of TRPM4 expression and the prognosis and/or the post-treatment reoccurrence of the disease was studied [190,191,196,203]. Several studies described the molecular mechanisms by which TRPM4 influences these diseases.…”

Section: The Role Of Trpm4 In Cancermentioning

confidence: 99%

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Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel—Part 2: TRPM4 in Health and Disease

et al. 2021

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Transient receptor potential melastatin 4 (TRPM4) is a unique member of the TRPM protein family and, similarly to TRPM5, is Ca2+ sensitive and permeable for monovalent but not divalent cations. It is widely expressed in many organs and is involved in several functions; it regulates membrane potential and Ca2+ homeostasis in both excitable and non-excitable cells. This part of the review discusses the currently available knowledge about the physiological and pathophysiological roles of TRPM4 in various tissues. These include the physiological functions of TRPM4 in the cells of the Langerhans islets of the pancreas, in various immune functions, in the regulation of vascular tone, in respiratory and other neuronal activities, in chemosensation, and in renal and cardiac physiology. TRPM4 contributes to pathological conditions such as overactive bladder, endothelial dysfunction, various types of malignant diseases and central nervous system conditions including stroke and injuries as well as in cardiac conditions such as arrhythmias, hypertrophy, and ischemia-reperfusion injuries. TRPM4 claims more and more attention and is likely to be the topic of research in the future.

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Differential effects of TRPM4 channel inhibitors on Guinea pig urinary bladder smooth muscle excitability and contractility: Novel 4‐chloro‐2‐[2‐(2‐chloro‐phenoxy)‐acetylamino]‐benzoic acid (CBA) versus classical 9‐phenanthrol

Malysz

Maxwell

Petkov

2022

Pharmacology Res & Perspec

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Abbreviations: BTP2, pyrazol-1-yl]phenyl]-4-methylthiadiazole-5-carboxamide, alias YM-58483; Ca V , voltage-gated Ca 2+ (channel); CBA, 4-chloro-2-[2-(2chloro-phenoxy)-acetylamino]-benzoic acid; ddH 2 0, double distilled H 2 0; EFS, electrical field stimulation; FFA, flufenamic acid; IK, intermediate conductance calcium activated K + (channel); K Ca 1.1, voltage and calcium activated large conductance K + (channel), alias BK or MaxiK + ; K V , voltage-gated K + (channel); Na V , voltage-gated Na + (channel); UBSM, urinary bladder smooth muscle; TRPM4, transient receptor potential melastatin type-4.

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Aberrant TRPM4 expression in MLL-rearranged acute myeloid leukemia and its blockade induces cell cycle arrest via AKT/GLI1/Cyclin D1 pathway

Cited by 13 publications

References 26 publications

TRPM4 in Cancer—A New Potential Drug Target

TRPM4 in Cancer—A New Potential Drug Target

Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel—Part 2: TRPM4 in Health and Disease

Differential effects of TRPM4 channel inhibitors on Guinea pig urinary bladder smooth muscle excitability and contractility: Novel 4‐chloro‐2‐[2‐(2‐chloro‐phenoxy)‐acetylamino]‐benzoic acid (CBA) versus classical 9‐phenanthrol

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