mTOR inhibition overcomes RSK3-mediated resistance to BET inhibitors in small cell lung cancer

Kumari, Anju; Gesumaria, Lisa; Liu, Yan-Jin; Hughitt, V. K.; Zhang, Xiaohu; Ceribelli, Michele; Wilson, Kelli; Klumpp‐Thomas, Carleen; Chen, Lu; McKnight, Crystal; Itkin, Zina; Thomas, Craig J.; Mock, Beverly A.; Schrump, David S.; Chen, Haobin

doi:10.1172/jci.insight.156657

Cited by 13 publications

(3 citation statements)

References 54 publications

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“…Reduced IFN-γ levels can contribute to immune response suppression, thereby promoting liver and lung metastasis of colon cancer cells. T-bet phosphorylation at serines 498 and 502 mediated by RSK2 was important for suppressing colon cancer cell metastasis and CRC tumor growth, as it positively regulated the RSK2/T-bet/IFN-γ signaling pathway [30] . Additionally, Ye et al concluded that the RSK4 gene may inhibit the epithelial-mesenchymal transition (EMT) in the CRC context and metastasis of CRC cells, which may indicate the potential of RSK4 as an inhibitor of tumor progression and metastasis [38] .…”

Section: The Rsk Family In Crc Metastasismentioning

confidence: 98%

“…Decreased expression RSK1 Lung adenocarcinomas [14] , Leukemia [20] , CRC [21] , Renal cancer [22] , Ovarian cancer [23] , Glioma [24] Breast cancer [25] RSK2 Glioma [24] , Breast cancer [25,26] , Lung cancer [27] , Leukemia [28] , Ovarian cancer [29] CRC [30] RSK3 -Breast cancer [25] , Lung cancer [31] , Ovarian cancer [32] RSK4 Renal cancer [33] , Glioma [34,35] Breast cancer [36] , Lung cancer [37] , CRC [38] , Leukemia [39] , Esophageal cancer [40] , Ovarian cancer [41] CRC: Colorectal cancer. dependent manner [42] .…”

Section: Increased Expressionmentioning

confidence: 99%

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Regulation and function of the RSK family in colorectal cancer

Wang,

Han,

Lei

et al. 2024

J Cancer Metastasis Treat

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P90 Ribosomal S6 Kinases (RSKs) constitute a class of Serine/Threonine (Ser/Thr) protein kinases and play a critical role as downstream targets in the Raf/MEK/ERK signaling pathway. Gaining insight into the biological function of RSK family proteins, given their functions in various tumors, is vital. The RSK family is involved in the regulation of cellular functions including cell proliferation, motility, invasion, and survival. The RSK family comprises four human isoforms (RSK1, RSK2, RSK3, and RSK4). The activation of RSK protein kinases is mediated through direct phosphorylation by extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphoinositide-dependent kinase 1 (PDK1) after the Ras/MAPK (mitogen-activated protein kinase) pathway is activated. Recent evidence suggests that RSK family proteins promote the onset and metastasis of cancer, leading to the association of the protein expression of these kinases with various cancer types, such as colorectal cancer (CRC), breast cancer, lung cancer, kidney cancer, leukemia, esophageal squamous cell carcinoma, ovarian cancer, glioma, and endometrial cancer. In this review, we summarize the latest research on the RSK family, focusing on its role in patients with CRC, along with associated treatment challenges and limitations. This information enhances our comprehension of the regulation and function of RSK family proteins, highlighting their potential as both clinical biomarkers for diagnosing CRC and targets for molecular therapeutic interventions in the future.

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Section: The Rsk Family In Crc Metastasismentioning

confidence: 98%

Section: Increased Expressionmentioning

confidence: 99%

Regulation and function of the RSK family in colorectal cancer

Wang,

Han,

Lei

et al. 2024

J Cancer Metastasis Treat

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“…JQ1 with the chemotherapeutic agent paclitaxel reversed this upregulation and induced apoptosis. Another study found that BETi upregulate the mTOR upstream kinase RSK3, leading to resistance to apoptosis in SCLC cells (Kumari et al, 2023). The combination of BETi and mTOR inhibitors disrupted mTOR signaling and displayed superior anti-cancer activity than any single drug in vitro (JQ1/rapamycin) and in vivo (NHWD870/ everolimus) assays.…”

Section: Combination Therapymentioning

confidence: 99%

Pathogenic role of super-enhancers as potential therapeutic targets in lung cancer

Yao,

Song,

Jiao

2024

Front. Pharmacol.

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Lung cancer is still one of the deadliest malignancies today, and most patients with advanced lung cancer pass away from disease progression that is uncontrollable by medications. Super-enhancers (SEs) are large clusters of enhancers in the genome’s non-coding sequences that actively trigger transcription. Although SEs have just been identified over the past 10 years, their intricate structure and crucial role in determining cell identity and promoting tumorigenesis and progression are increasingly coming to light. Here, we review the structural composition of SEs, the auto-regulatory circuits, the control mechanisms of downstream genes and pathways, and the characterization of subgroups classified according to SEs in lung cancer. Additionally, we discuss the therapeutic targets, several small-molecule inhibitors, and available treatment options for SEs in lung cancer. Combination therapies have demonstrated considerable advantages in preclinical models, and we anticipate that these drugs will soon enter clinical studies and benefit patients.

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