Targeting BAP1 with small compound inhibitor for colon cancer treatment.

BRCA1-associated protein-1 (BAP1) is a ubiquitin C-terminal hydrolase domain-containing deubiquitinase. The gene encoding BAP1 is mutated in various human cancers, including mesothelioma, uveal melanoma and renal cell carcinoma. BAP1 plays roles in many cancer-related cellular functions, including cell proliferation, cell death, and nuclear processes crucial for genome stability, such as DNA repair and replication. While these findings suggest that BAP1 functions as a tumor suppressor, recent data also suggest that BAP1 might play tumor-promoting roles in certain cancers, such as breast cancer and hematopoietic malignancies. Here, we show that BAP1 is upregulated in colon cancer cells and tissues and that BAP1 depletion reduces colon cancer cell proliferation and tumor growth. BAP1 contributes to colon cancer cell proliferation by accelerating DNA replication and suppressing replication stress and concomitant apoptosis. A recently identified BAP1 inhibitor, TG2-179-1, which seems to covalently bind to the active site of BAP1, exhibits potent cytotoxic activity against colon cancer cells, with half-maximal inhibitory concentrations of less than 10 µM, and inhibits colon tumor growth. TG2-179-1 exerts cytotoxic activity by targeting BAP1, leading to defective replication and increased apoptosis. This work therefore shows that BAP1 acts oncogenically in colon cancer and is a potential therapeutic target for this cancer. Our work also suggests that TG2-179-1 can be developed as a potential therapeutic agent for colon cancer.

Diasporic Condition: Jane Jin Kaisen's Strange Meetings And Its Tracing Of Ambiguous Colonial Vestiges.

Jane Jin Kaisen's 2017 video work, Strange Meetings, documents the inside and surroundings of a former STD (sexually transmittable disease) treatment center for prohibiting the spread of STD among the U.S. GIs as part of the "Clean-Up Campaign" during the 1970s, located near Soyo Mountain in Dongducheon-si, South Korea. This essay questions how the figure of diaspora expressed through art helps trace the contemporary vestiges of colonial violence, and raises a fundamental question to the notion of national community. I argue that Strange Meetings critically revisits South Korea's nationalist historiography by foregrounding a metaphor of diaspora that, according to Stuart Hall, while signaling its "permanent instability" as a historical marker, exceeds binary structures of representation: such as, literal/figurative, past/present, and them/us. In Strange Meetings, diasporic identities are kaksori, a cross-dressed wandering performer, a "vocal" survivor of the camp town prostitution, and the art work itself that is multidimensional, alterable, and globetrotting installation - all of which, I conceptualize borrowing Ann L. Stoler's terms, constitute "ambiguous colonial vestiges." The attempts to find fault of the nationalist and misogynous hegemony from within, especially through subaltern voices, have been greatly constrained in South Korea since the Korean War (1950-3). Strange Meetings, however, shows that when they are set in motion, they lend one of the most powerful impetuses for the feminist critique against the intimate tie between the U.S.'s neocolonial occupation of South Korea and Korean patriarchal nationalism.