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Updated: Apr 22, 2026
Single-Molecule Localization Microscopy of Membrane Proteins using Single-Antibody Labeling
Published on: March 20, 2026
CD74 interferes with the expression of fas receptor on the surface of lymphoma cells
Zuzana Berkova1, Shu Wang2, Xue Ao3
1Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA. zberkova@mdanderson.org.
Background:
Resistance to Fas-mediated apoptosis limits the efficacy of currently available chemotherapy regimens. We identified CD74, which is known to be overexpressed in hematological malignancies, as one of the factors interfering with Fas-mediated apoptosis.
Methods:
CD74 expression was suppressed in human B-lymphoma cell lines, BJAB and Raji, by either transduction with lentivirus particles or transfection with episomal vector, both encoding CD74-specific shRNAs or non-target shRNA. Effect of CD74 expression on Fas signaling was evaluated by comparing survival of mice hydrodynamically transfected with vector encoding full-length CD74 or empty vector. Sensitivity of cells with suppressed CD74 expression to FasL, edelfosine, doxorubicin, and a humanized CD74-specific antibody, milatuzumab, was evaluated by flow cytometry and compared to control cells. Fas signaling in response to FasL stimulation and the expression of Fas signaling components were evaluated by Western blot. Surface expression of Fas was detected by flow cytometry.
Results:
We determined that cells with suppressed CD74 are more sensitive to FasL-induced apoptosis and Fas signaling-dependent chemotherapies, edelfosine and doxorubicin, than control CD74-expressing cells. On the other hand, expression of full-length CD74 in livers protected the mice from a lethal challenge with agonistic anti-Fas antibody Jo2. A detailed analysis of Fas signaling in cells lacking CD74 and control cells revealed increased cleavage/activation of pro-caspase-8 and corresponding enhancement of caspase-3 activation in the absence of CD74, suggesting that CD74 affects the immediate early steps in Fas signaling at the plasma membrane. Cells with suppressed CD74 expression showed increased staining of Fas receptor on their surface. Pre-treatment with milatuzumab sensitized BJAB cells to Fas-mediated apoptosis.
Conclusion:
We anticipate that specific targeting of the CD74 on the cell surface will sensitize CD74-expressing cancer cells to Fas-mediated apoptosis, and thus will increase effectiveness of chemotherapy regimens for hematological malignancies.
Insights
Targeting CD74 (Cluster of Differentiation 74) can overcome resistance to Fas-mediated apoptosis in cancer. Suppressing CD74 enhances sensitivity to chemotherapy and FasL, improving treatment efficacy for hematological malignancies.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Resistance to Fas-mediated apoptosis is a key challenge in cancer chemotherapy.
- CD74 (Cluster of Differentiation 74) is overexpressed in hematological malignancies and interferes with Fas-mediated apoptosis.
Purpose of the Study:
- To investigate the role of CD74 in regulating Fas-mediated apoptosis.
- To determine if targeting CD74 can enhance cancer cell sensitivity to apoptosis and chemotherapy.
Main Methods:
- CD74 expression was suppressed in B-lymphoma cell lines using shRNAs delivered via lentivirus or episomal vectors.
- Sensitivity to FasL, edelfosine, doxorubicin, and milatuzumab was assessed in CD74-suppressed cells.
- Fas signaling pathway components and Fas receptor surface expression were analyzed by Western blot and flow cytometry.
Main Results:
- Suppression of CD74 increased sensitivity to FasL-induced apoptosis and chemotherapy (edelfosine, doxorubicin).
- CD74 expression protected mice from anti-Fas antibody-induced apoptosis.
- Lack of CD74 enhanced caspase-8 and caspase-3 activation, indicating improved early Fas signaling.
- CD74 suppression increased surface Fas receptor expression and sensitivity to milatuzumab.
Conclusions:
- Targeting cell surface CD74 can sensitize cancer cells to Fas-mediated apoptosis.
- This approach holds promise for increasing the effectiveness of chemotherapy regimens for hematological malignancies.
