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Oncogenic Signaling Shaped by a Golgi Trafficking Protein Pair
Oncogenic Signaling Shaped by a Golgi Trafficking Protein Pair
A new study in Science Signaling identifies a previously overlooked control point in receptor tyrosine kinase (RTK) signaling, one that operates not at the plasma membrane, but at the Golgi. The research, published as “Oncogenic receptor tyrosine kinase signaling is driven by the Golgi protein GOLPH3 and its interaction with MYO18A,” reveals that the Golgi‑localized proteins GOLPH3 and MYO18A act together to route RTKs to the cell surface, thereby setting the strength of growth‑factor signaling across multiple pathways.
The work was led by Kyle Starost and colleagues at Case Western Reserve University School of Medicine and the University of California, San Diego. Their findings help explain why GOLPH3 is frequently amplified in human cancers and why its overexpression correlates with poor prognosis across tumor types.
RTKs such as EGFR, insulin receptor, and PDGFR are central drivers of proliferation and survival in many cancers. Although RTK inhibitors are widely used clinically, resistance often emerges, underscoring the need for alternative strategies that modulate signaling upstream of the receptor. The new study identifies one such upstream node: the delivery of RTKs from the Golgi to the plasma membrane.
Using an unbiased signaling analysis, the team found that siRNA knockdown of GOLPH3 or MYO18A impaired phosphorylation of EGFR at Tyr1068 and Tyr1086, as well as downstream AKT and ERK signaling. These defects persisted even when PI3K/AKT/mTOR signaling was pharmacologically blocked, demonstrating that GOLPH3 acts directly at the receptor level rather than through mTOR modulation.
To pinpoint the mechanism, the researchers turned to trafficking assays. Imaging of endogenous EGFR showed that loss of GOLPH3 or MYO18A caused the receptor to accumulate in intracellular puncta rather than at the plasma membrane. A quantitative PDGFR‑GFP surface‑delivery assay confirmed that both proteins are required for Golgi‑to‑surface transport. Treatment with brefeldin A or golgicide A, which disrupt Golgi structure, produced similar reductions in surface receptor levels, reinforcing the conclusion that the GOLPH3–MYO18A complex is essential for RTK delivery.
Overexpression experiments completed the mechanistic picture. Increasing GOLPH3 or MYO18A levels enhanced EGF‑stimulated phosphorylation of EGFR and AKT, while a GOLPH3 mutant unable to bind PI4P failed to do so. These results position the GOLPH3–MYO18A complex as a central determinant of RTK availability at the cell surface.
The authors wrote, “The GOLPH3-MYO18A complex at the Golgi apparatus was required and rate-limiting for RTK signaling across the cell types and receptors assessed.” The findings suggest that targeting Golgi‑based trafficking machinery could offer a new therapeutic angle for tumors that rely on hyperactive RTK signaling or have developed resistance to RTK inhibitors.
The post Oncogenic Signaling Shaped by a Golgi Trafficking Protein Pair appeared first on GEN – Genetic Engineering and Biotechnology News.
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STAT+: Up and down the ladder: The latest comings and goings
Hired someone new and exciting? Promoted a rising star? Finally solved that hard-to-fill spot? Share the news with us, and we’ll share it with others. That’s right. Send us your changes, and we’ll find a home for them. Don’t be shy. Everyone wants to know who is coming and going.
And here is our regular feature in which we highlight a different person each week. This time around, we note that AstronauTx hired Michelle Mellion as chief medical officer. Previously, she held the same role at PepGen and EveryONE Medicines.
But all work and no play can make for a dull chief medical officer.
Hired someone new and exciting? Promoted a rising star? Finally solved that hard-to-fill spot? Share the news with us, and we’ll share it with others. That’s right. Send us your changes, and we’ll find a home for them. Don’t be shy. Everyone wants to know who is coming and going.
And here is our regular feature in which we highlight a different person each week. This time around, we note that AstronauTx hired Michelle Mellion as chief medical officer. Previously, she held the same role at PepGen and EveryONE Medicines.
But all work and no play can make for a dull chief medical officer.
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STAT+: Pharmalittle: We’re reading about a discontinued cancer drug, a Novo security breach, and more
And so, another working week will soon draw to a close. Not a moment too soon, yes? This is, you may recall, our treasured signal to daydream about weekend plans. Our agenda includes promenading with the official mascots, catching another round of live musical vibes here and there, and taking pride in some folks who are dear to us. We also hope to hold yet another listening party, where the rotation will likely include this, this, this, this and this. And what about you? This is a wonderful time of year to sample the many outdoor activities popping up — street fairs, festivals, and all sorts of gatherings can be sampled. If the weather fails to cooperate, though, you could curl up with a good book, sit in front of the telly to take in one or more sporting events, or plan a needed getaway. If none of this strikes your fancy, you could simply park yourself somewhere comfortable for a while and remain zen. Well, whatever you do, have a grand time. But be safe. Enjoy, and see you soon. …
In a rare move, the nonprofit organization Blood Cancer United announced it was buying the remaining supplies of Luvelta, a discontinued investigational cancer drug, STAT reports. As part of the transaction, Blood Cancer United, previously known as the Leukemia & Lymphoma Society, also will acquire the investigational new drug designation and manage the compassionate-use program for children with a rare form of blood cancer, distributing the medication to patients at no cost while supplies last. Sutro Biopharma discontinued development in March 2025 and also eliminated a compassionate use program.
Novo Nordisk identified a security incident in which certain information, including patient data from some clinical trials, was copied externally without authorization from its internal IT systems, Reuters notes. The company said it launched a probe with the assistance of external cybersecurity experts and is in contact with the relevant authorities. The potential categories of personal data affected may include patient ID, year of birth, sex, and health or immunogenicity data among others. Novo did not provide further details, but does not believe the incident will enable any third party to identify participants in its clinical trials.
And so, another working week will soon draw to a close. Not a moment too soon, yes? This is, you may recall, our treasured signal to daydream about weekend plans. Our agenda includes promenading with the official mascots, catching another round of live musical vibes here and there, and taking pride in some folks who are dear to us. We also hope to hold yet another listening party, where the rotation will likely include this, this, this, this and this. And what about you? This is a wonderful time of year to sample the many outdoor activities popping up — street fairs, festivals, and all sorts of gatherings can be sampled. If the weather fails to cooperate, though, you could curl up with a good book, sit in front of the telly to take in one or more sporting events, or plan a needed getaway. If none of this strikes your fancy, you could simply park yourself somewhere comfortable for a while and remain zen. Well, whatever you do, have a grand time. But be safe. Enjoy, and see you soon. …
In a rare move, the nonprofit organization Blood Cancer United announced it was buying the remaining supplies of Luvelta, a discontinued investigational cancer drug, STAT reports. As part of the transaction, Blood Cancer United, previously known as the Leukemia & Lymphoma Society, also will acquire the investigational new drug designation and manage the compassionate-use program for children with a rare form of blood cancer, distributing the medication to patients at no cost while supplies last. Sutro Biopharma discontinued development in March 2025 and also eliminated a compassionate use program.
Novo Nordisk identified a security incident in which certain information, including patient data from some clinical trials, was copied externally without authorization from its internal IT systems, Reuters notes. The company said it launched a probe with the assistance of external cybersecurity experts and is in contact with the relevant authorities. The potential categories of personal data affected may include patient ID, year of birth, sex, and health or immunogenicity data among others. Novo did not provide further details, but does not believe the incident will enable any third party to identify participants in its clinical trials.
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