Publications (** denotes equal contribution, # denotes co-corresponding author)

2017

sm”FISH”ing for Hedgehog
Michael L. Drummond and Scott X. Atwood
Journal of Investigative Dermatology. 2017. 137(1):13-5.
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Cell-selective bioorthogonal metabolic labeling of RNA
Kim Nguyen**, Michael Fazio**, Miles Kubota, Sarah Nainar, Chao Feng, Xiang Li, Scott X. Atwood, Timothy W. Bredy, Robert C. Spitale
Journal of the American Chemical Society. 2017. 139(6):2148-51.
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Atypical Protein Kinase C - Histone Deacetylase 1 inhibitors cooperate in basal cell carcinoma treatment
Amar N. Mirza, Micah A. Fry, Nicole M. Urman, Scott X. Atwood, Jon Roffey, Gregory R. Ott, Bin Chen, Alex Lee, Alexander S. Brown, Sumaira Z. Aasi, Tyler Hollmig, Mark A. Ator, Bruce D. Dorsey, Bruce R. Ruggeri, Craig A. Zificsak, Marina Sirota, Jean Y. Tang, Atul Butte, Ervin Epstein, Kavita Y. Sarin#, Anthony E. Oro#
JCI Insight. 2017. doi.org/10.1172/jci.insight.97071.
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The brighter side of UV-induced mutations in basal cell carcinoma.
Tuyen T.L. Nguyen and Scott X. Atwood
Submitted.

Cdc42 restricts primary cilia length through actin regulation to control Hedgehog signaling
Michael L. Drummond, Mischa Li, Tuyen T. Nguyen, Shaun Cruz, Anthony E. Oro#, Scott X. Atwood#
Submitted.

2016

Tumor-derived Suppressor of Fused mutations reveal Hedgehog pathway interactions
Nicole M. Urman, Amar Mirza, Scott X. Atwood, Ramon J. Whitson, Kavita Y. Sarin, Jean Y. Tang, Anthony E. Oro
Plos One. 2016. 11(12):e0168031.
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Combined treatment with arsenic trioxide and itraconazole inhibits the Hedgehog pathway in patients with refractory metastatic basal cell carcinoma: results from a pilot trial
Mina S. Ally, Katherine Ransohoff, Kavita Sarin, Scott X. Atwood, Melika Rezaee, Irene Bailey-Healy, Jynho Kim, Philip A. Beachy, Anne Lynn S. Chang, Anthony Oro, Jean Y. Tang, A. Dimitrios Colevas
JAMA Dermatology. 2016. 152(4):452-6.
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2015

Smoothened variants explain the majority of drug resistance in basal cell carcinoma
Scott X. Atwood**, Kavita Y. Sarin**, Ramon J. Whitson, Jiang R. Li, Geurim Kim, Melika Rezaee, Mina S. Ally, Jinah Kim, Catherine Yao, Anne L.S. Chang, Anthony E. Oro#, Jean Y. Tang#
Cancer Cell. 2015. 27(3):342-53.
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Preview in Cancer Cell
Comment in Cancer Discovery
Comment in NEJM Journal Watch
Highlight in Cancer Research

Advanced basal cell carcinomas (BCCs) frequently acquire resistance to Smoothened (SMO) inhibitors through unknown mechanisms. Here, we identify SMO mutations in 50% (22/44) of resistant BCCs and show that these mutations maintain Hedgehog signaling in the presence of SMO inhibitors. Alterations include four ligand binding pocket mutations defining sites of inhibitor binding and four variants confering constitutive activity and inhibitor resistance, illuminating pivotal residues that ensure receptor autoinhibition. These genetic alterations suggest that SMO functions similarly to other class A GPCRs despite less than 10% sequence identity. In the presence of a SMO inhibitor, tumor cells containing both classes of SMO mutants effectively compete against cells containing wild type SMO. Finally, we show that both classes of SMO variants respond to aPKC-ι/λ or GLI2 inhibitors that operate downstream of SMO, setting the stage for the clinical use of GLI antagonists.

Rolling the genetic dice: neutral and deleterious Smoothened mutations in drug-resistant basal cell carcinoma
Scott X. Atwood, Kavita Y. Sarin, Jiang R. Li, Catherine Yao, Nicole M. Urman, Anne L.S. Chang, Jean Y. Tang, Anthony E. Oro
Journal of Investigative Dermatology. 2015. 135(8):2138-41.
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RAS/MAPK activation drives resistance to Smo inhibition, metastasis and tumor evolution in Shh pathway-dependent tumors
Xuesong Zhao, Tatyana Ponomaryov, Kimberly J. Ornell, Pengcheng Zhou, Sukriti K. Dabral, Ekaterina Pak, Wei Li, Scott X. Atwood, Ramon J. Whitson, Anne Lynn S. Chang, Jiang Li, Anthony E. Oro, Jennifer A. Chan, Joseph F. Kelleher, Rosalind A. Segal
Cancer Research. 2015. 75(17):3623-35.
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Mutations in the kinetochore gene KNSTRN in basal cell carcinoma
Prajakta Jaju, Christie B. Nguyen, Angela M. Mah, Scott X. Atwood, Jiang R. Li, Amin Zia, Anne L.S. Chang, Anthony E. Oro, Jean Y. Tang, Cari S. Lee, Kavita Y. Sarin
Journal of Investigative Dermatology. 2015. 135(12):3197-200.
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2014 and earlier

Advanced treatment for basal cell carcinomas
Scott X. Atwood, Ramon J. Whitson, Anthony E. Oro
Cold Spring Harbor Perspectives in Medicine. 2014. 4(7):a013581.
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"Atypical" regulation of Hedgehog-dependent cancer
Scott X. Atwood and Anthony E. Oro
Cancer Cell. 2014. 25(2):133-4.
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Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition
Yujie Tang, Sharareh Gholamin, Simone Schubert, Minde I. Willardson, Alex Lee, Pratiti Bandopadhayay, Guillame Bergthold, Sabran Masoud, Brian Nguyen, Nujsaubnusi Vue, Brianna Balansay, Furong Yu, Sekyung Oh, Pamelyn Woo, Spenser Chen, Anitha Ponnuswami, Michelle Monje, Scott X. Atwood, Ramon J. Whitson, Siddhartha Mitra, Samuel H. Cheshier, Jun Qi, Rameen Beroukhim, Jean Y. Tang, Rob Wechsler-Reya, Anthony E. Oro, Brian A. Link, James E. Bradner, Yoon-Jae Cho
Nature Medicine. 2014. 20(7):732-40.
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Comment in SciBX PDF

Identification of genes promoting skin youthfulness by genome-wide association study
Anne L.S. Chang, Gil Atzmon, Aviv Bergman, Samantha Brugmann, Scott X. Atwood, Howard Y. Chang, Nir Barzilai
Journal of Investigative Dermatology. 2014. 134(3):651-7.
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GLI activation by atypical protein kinase C iota/lambda regulates the growth of basal cell carcinomas
Scott X. Atwood#, Mischa Li, Alex Lee, Jean Y. Tang, Anthony E. Oro#
Nature. 2013. 494(7438):484-8.
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Comment in Cancer Discovery
Comment in SciBX
Editors' Choice in Science Signaling
Highlight in Nature Reviews Cancer
F1000 Prime Recommendation
Reviewed in Acta Biochimica Biophysica Sinica

Growth of basal cell carcinomas (BCCs) requires high levels of hedgehog (HH) signalling through the transcription factor GLI1. Although inhibitors of membrane protein smoothened (SMO) effectively suppress HH signalling, early tumour resistance illustrates the need for additional downstream targets for therapy. Here we identify atypical protein kinase C iota/lambda (aPKC) as a novel GLI regulator in mammals. aPKC and its polarity signalling partners co-localize at the centrosome and form a complex with missing-in-metastasis (MIM), a scaffolding protein that potentiates HH signalling. Genetic or pharmacological loss of aPKC function blocks HH signalling and proliferation of BCC cells. Prkci is a HH target gene that forms a positive feedback loop with GLI and exists at increased levels in BCCs. Genome-wide transcriptional profiling shows that aPKC and SMO control the expression of similar genes in tumour cells. aPKC functions downstream of SMO to phosphorylate and activate GLI1, resulting in maximal DNA binding and transcriptional activation. Activated aPKC is upregulated in SMO-inhibitor-resistant tumours and targeting aPKC suppresses signalling and growth of resistant BCC cell lines. These results demonstrate that aPKC is critical for HH-dependent processes and implicates aPKC as a new, tumour-selective therapeutic target for the treatment of SMO inhibitor-resistant cancers.

Rapid genetic analysis of epithelial-mesenchymal signaling during hair regeneration
Wei-Meng Woo**, Scott X. Atwood**, Hansen H. Zhen, Anthony E. Oro
Journal of Visualized Experiments. 2013. (72):e4344.
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"Patch"ing up our tumor signaling knowledge
Scott X. Atwood**, Ramon J. Whitson**, Anthony E. Oro
Journal of Investigative Dermatology. 2013. 133(5):1131-3.
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Surgical excision after neoadjuvant therapy with vismodegib for a locally advanced basal cell carcinoma and resistant basal cell carcinomas in Gorlin syndrome
Anne L.S. Chang, Scott X. Atwood, Danielle M. Tartar, Anthony E. Oro
JAMA Dermatology. 2013. 149(5):639-41.
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Hedgehog pathway inhibition and the race against tumor evolution
Scott X. Atwood, Anne L.S. Chang, Anthony E. Oro
Journal of Cell Biology. 2012. 199(2):193-7.
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Partitioning-defective protein 6 (Par-6) activates atypical protein kinase C (aPKC) by pseudosubstrate displacement
Chiharu Graybill, Brett Wee, Scott X. Atwood, Kenneth E. Prehoda
Journal of Biological Chemistry. 2012. 287(25):21003-11.
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MIM and Cortactin antagonism regulates ciliogenesis and Hedgehog signaling
Marina Bershteyn, Scott X. Atwood, Wei-Meng Woo, Mischa Li, Anthony E. Oro
Developmental Cell. 2010. 19(2):270-83.
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Cover article
Preview in Developmental Cell

aPKC phosphorylates Miranda to polarize fate determinants during neuroblast asymmetric cell division
Scott X. Atwood and Kenneth E. Prehoda
Current Biology. 2009. 19(9):723-9.
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Cdc42 acts downstream of Bazooka to regulate neuroblast polarity through Par-6-aPKC
Scott X. Atwood, Chiswili Chabu, Rhiannon R. Penkert, Chris Q. Doe, Kenneth E. Prehoda
Journal of Cell Science. 2007. 120(Pt 18):3200-6.
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F1000 Prime Recommendation