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Your search keyword '"Rachel Y. Chow"' showing total 2 results
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2 results on '"Rachel Y. Chow"'

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

Author

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

Subjects
basal cell carcinoma, hedgehog, PI3K - AKT pathway, p21, atypical PKCι, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Basal cell carcinoma (BCC) is a locally invasive epithelial cancer that is primarily driven by the Hedgehog (HH) pathway. Advanced BCCs are a critical subset of BCCs that frequently acquire resistance to Smoothened (SMO) inhibitors and identifying pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify a PI3K pathway expression signature in BCC. Pharmacological inhibition of PI3K activity in BCC cells significantly reduces cell proliferation and HH signaling. However, treatment of Ptch1fl/fl; Gli1-CreERT2 mouse BCCs with the PI3K inhibitor BKM120 results in a reduction of tumor cell growth with no significant effect on HH signaling. Downstream PI3K components aPKC and Akt1 showed a reduction in active protein, whereas their substrate, cyclin-dependent kinase inhibitor p21, showed a concomitant increase in protein stability. Our results suggest that PI3K promotes BCC tumor growth by kinase-induced p21 degradation without altering HH signaling.

Published
2021
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2. MTOR promotes basal cell carcinoma growth through atypical PKC

Author

Rachel Y. Chow, Daniel P. Cedeno, Scott X. Atwood, Taylor M. Levee, Linda Doan, and Gurleen Kaur

Subjects
0301 basic medicine, Skin Neoplasms, Basal Cell, Biochemistry, Mice, 030207 dermatology & venereal diseases, 0302 clinical medicine, skin and connective tissue diseases, Protein Kinase C, Cancer, Tumor, integumentary system, Triazines, Chemistry, TOR Serine-Threonine Kinases, Imidazoles, SMO antagonist, Immunohistochemistry, Hedgehog signaling pathway, Patched-1 Receptor, cancer therapy, Sequence Analysis, Atypical pkc, Signal Transduction, medicine.drug, animal structures, Clinical Sciences, Antineoplastic Agents, Dermatology, cancer heterogeneity, Zinc Finger Protein GLI1, Article, Cell Line, 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, Humans, Tumor growth, Hedgehog Proteins, Basal cell carcinoma, Everolimus, Molecular Biology, Hedgehog, PI3K/AKT/mTOR pathway, Cell Proliferation, Sirolimus, drug resistance, Sequence Analysis, RNA, Cell growth, Dermatology & Venereal Diseases, Carcinoma, fungi, medicine.disease, 030104 developmental biology, PTCH1, Carcinoma, Basal Cell, Hedgehog signalling, Cancer research, RNA, Immunostaining
Abstract

Advanced basal cell carcinomas (BCCs) are driven by the Hedgehog (HH) pathway and often possess inherent resistance to SMO inhibitors. Identifying and targeting pathways that bypass SMO could provide alternative treatments. Here, we use a combination of RNA-sequencing analysis of advanced BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify an MTOR signature in BCC. Pharmacological inhibition of MTOR activity in BCC cells significantly reduces cell proliferation without affecting HH signaling. Similarly, treatment ofPtch1fl/fl;Gli1-CreERT2mice with everolimus reduces tumor growth and aPKC activity, suggesting that MTOR promotes tumor growth by activating aPKC and demonstrating that suppressing MTOR could be a promising target for BCC patients.

Published
2020

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