PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation

Chow, Rachel Y.; Jeon, Ung Seop; Levee, Taylor M.; Kaur, Gurleen; Cedeno, Daniel P.; Doan, Linda; Atwood, Scott X.

doi:10.3389/fonc.2021.668247

Cited by 7 publications

(3 citation statements)

References 69 publications

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“…However, SMO mutations driving drug resistance are common, and up to 21% of patients treated with vismodegib were found to undergo tumor regrowth during treatment ( 3 ). Additional pathways that contribute to BCC drug resistance include phosphatidylinositol 3-kinase (PI3K)/MTOR (Mammalian target of rapamycin) ( 4 , 5 ), WNT ( 6 ), aPKC ι/λ ( 7 ), NOTCH1 ( 8 ), RAS/MAPK ( 9 , 10 ), and activation of MRTF ( 11 , 12 ), to name a few. New therapeutic options are needed to treat advanced BCC.…”

Section: Introductionmentioning

confidence: 99%

Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment

et al. 2022

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How basal cell carcinoma (BCC) interacts with its tumor microenvironment to promote growth is unclear. We use singe-cell RNA sequencing to define the human BCC ecosystem and discriminate between normal and malignant epithelial cells. We identify spatial biomarkers of tumors and their surrounding stroma that reinforce the heterogeneity of each tissue type. Combining pseudotime, RNA velocity–PAGA, cellular entropy, and regulon analysis in stromal cells reveals a cancer-specific rewiring of fibroblasts, where STAT1, TGF-β, and inflammatory signals induce a noncanonical WNT5A program that maintains the stromal inflammatory state. Cell-cell communication modeling suggests that tumors respond to the sudden burst of fibroblast-specific inflammatory signaling pathways by producing heat shock proteins, whose expression we validated in situ. Last, dose-dependent treatment with an HSP70 inhibitor suppresses in vitro vismodegib-resistant BCC cell growth, Hedgehog signaling, and in vivo tumor growth in a BCC mouse model, validating HSP70’s essential role in tumor growth and reinforcing the critical nature of tumor microenvironment cross-talk in BCC progression.

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Section: Introductionmentioning

confidence: 99%

Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment

et al. 2022

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“…Chow et al . 9 have demonstrated that the phosphatidylinositol 3-kinase (PI3K) pathway is essential for promoting tumor cell survival and proliferation. Therefore, the disorder of lipid metabolism and the development of tumors are closely intertwined and may impact the biological characteristics of cancer cells, such as proliferation, metastasis, and drug resistance, ultimately affecting the prognosis of the tumor.…”

Section: Lipid Metabolism and Pcamentioning

confidence: 99%

Lipid metabolism, amino acid metabolism, and prostate cancer: a crucial metabolic journey

Chen,

Xu,

Wang

et al. 2023

Asian Journal of Andrology

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Prostate cancer (PCa) is one of the most common malignancies in males worldwide, and its development and progression involve the regulation of multiple metabolic pathways. Alterations in lipid metabolism affect the proliferation and metastatic capabilities of PCa cells. Cancer cells increase lipid synthesis and regulate fatty acid oxidation to meet their growth and energy demands. Similarly, changes occur in amino acid metabolism in PCa. Cancer cells exhibit an increased demand for specific amino acids, and they regulate amino acid transport and metabolic pathways to fulfill their proliferation and survival requirements. These changes are closely associated with disease progression and treatment response in PCa cells. Therefore, a comprehensive investigation of the metabolic characteristics of PCa is expected to offer novel insights and approaches for the early diagnosis and treatment of this disease.

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“…Treatment of murine keratinocytes and BCC cells with tazarotene significantly reduced Gli mRNA expression [ 157 , 161 ]. The PI3 kinase-AKT-mTOR pathway is also important for BCC pathogenesis, in part by dysregulating the cell cycle and promoting proliferation [ 162 ]. So et al demonstrated that tazarotene represses overactivation PI3 kinase-AKT-mTOR signaling in murine BCCs [ 163 ].…”

Section: The Molecular Mechanisms Of Retinoid Activity In Experimenta...mentioning

confidence: 99%

The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review

Ramchatesingh

Villarreal

Arcuri

et al. 2022

IJMS

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Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi’s sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.

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PI3K Promotes Basal Cell Carcinoma Growth Through Kinase-Induced p21 Degradation

Cited by 7 publications

References 69 publications

Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment

Single-cell analysis of human basal cell carcinoma reveals novel regulators of tumor growth and the tumor microenvironment

Lipid metabolism, amino acid metabolism, and prostate cancer: a crucial metabolic journey

The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review

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