Tumor Initiation and Maintenance Program

How cancer begins

Cells become cancerous after acquiring a series of mutations in their DNA, which occur as a result of exposure to radiation, cigarette smoke, dietary components or a genetic predisposition.

Mutations may intensify or eliminate the messages cells use to grow, stop growing or die. Cells then begin to divide too often and are unable to die, forming tumors. Identifying the mutations, signals and mechanisms that promote and sustain tumors creates new opportunities to target human cancer.

Director's statement

We’ve brought together scientists with expertise in developmental and stem cell biology with investigators who focus on RNA biology and the signaling pathways that regulate cell growth and cell fate. The diversity of our faculty members, along with our shared interests in what drives cancer cell growth, is fostering strong interactions that will lead to breakthrough treatments for brain, breast and prostate cancers, as well as melanoma and leukemia.

– Robert Wechsler-Reya, Ph.D., Program Director

Appointments

Publications

EGFR-Pak Signaling Selectively Regulates Glutamine Deprivation-Induced Macropinocytosis.

Lee SW, Zhang Y, Jung M, Cruz N, Alas B, Commisso C

Dev Cell 2019 Aug 5 ;50(3):381-392.e5

Lsd1 as a therapeutic target in Gfi1-activated medulloblastoma.

Lee C, Rudneva VA, Erkek S, Zapatka M, Chau LQ, Tacheva-Grigorova SK, Garancher A, Rusert JM, Aksoy O, Lea R, Mohammad HP, Wang J, Weiss WA, Grimes HL, Pfister SM, Northcott PA, Wechsler-Reya RJ

Nat Commun 2019 Jan 18 ;10(1):332

Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5^-/- mice.

Li Y, Tinoco R, Elmén L, Segota I, Xian Y, Fujita Y, Sahu A, Zarecki R, Marie K, Feng Y, Khateb A, Frederick DT, Ashkenazi SK, Kim H, Perez EG, Day CP, Segura Muñoz RS, Schmaltz R, Yooseph S, Tam MA, Zhang T, Avitan-Hersh E, Tzur L, Roizman S, Boyango I, Bar-Sela G, Orian A, Kaufman RJ, Bosenberg M, Goding CR, Baaten B, Levesque MP, Dummer R, Brown K, Merlino G, Ruppin E, Flaherty K, Ramer-Tait A, Long T, Peterson SN, Bradley LM, Ronai ZA

Nat Commun 2019 Apr 2 ;10(1):1492

Zika Virus Targets Glioblastoma Stem Cells through a SOX2-Integrin α<sub>v</sub>β<sub>5</sub> Axis.

Zhu Z, Mesci P, Bernatchez JA, Gimple RC, Wang X, Schafer ST, Wettersten HI, Beck S, Clark AE, Wu Q, Prager BC, Kim LJY, Dhanwani R, Sharma S, Garancher A, Weis SM, Mack SC, Negraes PD, Trujillo CA, Penalva LO, Feng J, Lan Z, Zhang R, Wessel AW, Dhawan S, Diamond MS, Chen CC, Wechsler-Reya RJ, Gage FH, Hu H, Siqueira-Neto JL, Muotri AR, Cheresh DA, Rich JN

Cell Stem Cell 2019 Dec 31 ;

Humanized Stem Cell Models of Pediatric Medulloblastoma Reveal an Oct4/mTOR Axis that Promotes Malignancy.

Čančer M, Hutter S, Holmberg KO, Rosén G, Sundström A, Tailor J, Bergström T, Garancher A, Essand M, Wechsler-Reya RJ, Falk A, Weishaupt H, Swartling FJ

Cell Stem Cell 2019 Dec 5 ;25(6):855-870.e11

Translational reprogramming marks adaptation to asparagine restriction in cancer.

Pathria G, Lee JS, Hasnis E, Tandoc K, Scott DA, Verma S, Feng Y, Larue L, Sahu AD, Topisirovic I, Ruppin E, Ronai ZA

Nat Cell Biol 2019 Dec ;21(12):1590-1603

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

Suzuki H, Kumar SA, Shuai S, Diaz-Navarro A, Gutierrez-Fernandez A, De Antonellis P, Cavalli FMG, Juraschka K, Farooq H, Shibahara I, Vladoiu MC, Zhang J, Abeysundara N, Przelicki D, Skowron P, Gauer N, Luu B, Daniels C, Wu X, Forget A, Momin A, Wang J, Dong W, Kim SK, Grajkowska WA, Jouvet A, Fèvre-Montange M, Garrè ML, Nageswara Rao AA, Giannini C, Kros JM, French PJ, Jabado N, Ng HK, Poon WS, Eberhart CG, Pollack IF, Olson JM, Weiss WA, Kumabe T, López-Aguilar E, Lach B, Massimino M, Van Meir EG, Rubin JB, Vibhakar R, Chambless LB, Kijima N, Klekner A, Bognár L, Chan JA, Faria CC, Ragoussis J, Pfister SM, Goldenberg A, Wechsler-Reya RJ, Bailey SD, Garzia L, Morrissy AS, Marra MA, Huang X, Malkin D, Ayrault O, Ramaswamy V, Puente XS, Calarco JA, Stein L, Taylor MD

Nature 2019 Oct ;574(7780):707-711

Recurrent non-coding U1-snRNA mutations drive cryptic splicing in Shh medulloblastoma.

Suzuki H, Kumar SA, Shuai S, Diaz-Navarro A, Gutierrez-Fernandez A, De Antonellis P, Cavalli FMG, Juraschka K, Farooq H, Shibahara I, Vladoiu MC, Zhang J, Abeysundara N, Przelicki D, Skowron P, Gauer N, Luu B, Daniels C, Wu X, Forget A, Momin A, Wang J, Dong W, Kim SK, Grajkowska WA, Jouvet A, Fèvre-Montange M, Garrè ML, Rao AAN, Giannini C, Kros JM, French PJ, Jabado N, Ng HK, Poon WS, Eberhart CG, Pollack IF, Olson JM, Weiss WA, Kumabe T, López-Aguilar E, Lach B, Massimino M, Van Meir EG, Rubin JB, Vibhakar R, Chambless LB, Kijima N, Klekner A, Bognár L, Chan JA, Faria CC, Ragoussis J, Pfister SM, Goldenberg A, Wechsler-Reya RJ, Bailey SD, Garzia L, Morrissy AS, Marra MA, Huang X, Malkin D, Ayrault O, Ramaswamy V, Puente XS, Calarco JA, Stein L, Taylor MD

Nature 2019 Oct 9 ;

Nilotinib, an approved leukemia drug, inhibits smoothened signaling in Hedgehog-dependent medulloblastoma.

Chahal KK, Li J, Kufareva I, Parle M, Durden DL, Wechsler-Reya RJ, Chen CC, Abagyan R

PLoS One 2019 ;14(9):e0214901

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